micro_mod5_ms1

• PARVOVIRIDAE 18-26
• POLYOMAVIRIDAE 45
• PAPILLOMAVIRIDAE 55
• ADENOVIRIDAE 70-90

• HERPESVIRIDAE 110-200
• HEPADNAVIRIDAE 42
• IRIDOVIRIDAE 125-300

POXVIRIDAE 100 x 240 x 300

• PICORNAVIRIDAE 20-30
• CALICIVIRIDAE 35-40
• ASTROVIRIDAE 28-30
• REOVIRIDAE 60-80
• BIRNAVIRIDAE 60

• TOGAVIRIDAE 45-75 (RUBELLA - HELICAL)
• FLAVIVIRIDAE 30-40

• ARENAVIRIDAE 50-300
• BUNYAVIRIDAE 90-100
• CORONAVIRIDAE 80-160
• RETROVIRIDAE 100-120
• ORTHOMYXOVIRIDAE 80-120
• PARAMYXOVIRIDAE 150-300
• BORNAVIRIDAE ---
• RHABDOVIRIDAE 75-180
• FILOVIRIDAE (VARIABLE)

INFLUENZA VIRUSES

(-)ssRNA

8 SEGMENTS OF RNA & ENVELOPED

ENTRY - HEMAGGLUTININ (HA) AND NEURAMINADASE (N) ADSORBS TO CELL GLYCOPROTEIN RECEPTORS VIA SAILIC ACID MOLECULES

UNCOATING - ENDOCYTOSIS AND ENDOSOME ACIDIFICATION (PUMPS PROTONS THROUGH M2 CHANNEL; BLOCKED BY AMANTADINE & RIMANTADINE). VIRAL RNA INVADES NUCLEUS.

TRANSCRIPTION - ERROR PRONE VIRAL RNA DEPENDENT RNA POL (RdRP) PRIMES SEGMENTS TO MAKE mRNA

TRANSLATION - IN CYTOPLASM

REPLICATION - BLAH

ASSEMBLY - GENE SEGMENTS AND PROTS ASSEMBLE INTO PARTICLES AND GET HA & N BY BUDDING FROM PM

RESPIRATORY SYNCYTIAL, PAPRAINFLUENZA, MEASLES, MUMPS, METAPNEUMO, NIPAH, HENDRA

(-)ssRNA

NON-SEGMENTED & ENVELOPED

ENTRY - FUSION WITH PM. NO RECEPTOR MEDIATED ENDO.

UNCOATING - GENOME INJECTED INTO CYTOPLASM BY PM FUSION. NO NUCLEAR TRANSLOCATION.

TRANSCRIPTION - RdRP PRIMES TRANSCRIPTION TO MAKE mRNA.

TRANSLATION - BLAH

REPLICATION - BLAH

ASSEMBLY - ACQUIRE ENVELOPE BY BUDDING FROM PM

COMMON COLD, SARS

(+)ssRNA, NONSEG, ENV, HELICAL

• HCoV-OC43 (URT & CNS)
• HCoV-229E (URT)
• HCoV-SARS (LRT - ERROR-PRONE)

ENTRY - ACE II TO PM LEADS TO INJECTION OF GENOME INTO CYTOPLASM

TRANSLATION - PART OF GENOME TRANSLATED TO MAKE 1 LONG POLYPEPTIDE. VIRAL PROTEASES CLEAVE TO MAKE RdRP.

REPLICATION - TEMPLATE JUMPING; ERROR-PRONE

ASSEMBLY - ON ENDOPLASMIC RETICULUM GOLGI INTERMEDIATE COMPARTMENT (ERGIC)

BUDDING - FROM ERGIC THEN PASSES THROUGH PM

• STRUCTURAL PROTS:
• E - ENV
• M - MATRIX OR MEMBRANE
• S - SPIKE
• N - NUCLEOCAPSID

• NON-STRUCTURAL PROTS:
• RdRP - Nsp12 & 9
• PROTEASE - Nsp1, 2, & 5

• OTHER VIRUSES:
• FLAVI
• TOGA
• CALICI
• ASTRO

RETROVIRUSES (HIV & HUMAN T-LYMPHOTROPIC VIRUS)

LTRs ACT AS PROMOTERS

• PROTEINS:
• GAG PRECURSOR - STRUCT PROTS, MATRIX (MA), CAPSID (CA), AND NUCLEOCAPSID (NC) PROTS. VIRAL PROTEASE (PR).

POL PRECURSOR - REVERSE TRANSCRIPTASE (RT) AND INTEGRASE (IN).

ENV PRECURSOR - REQUIRED FOR CELL ENTRY. SURFACE (SU aka gp120) AND TRANSMEMBRANE (TM aka gp41).

2 RNA GENOMES (LENTI)

ENTRY - ENV PROT gp120 ATTACHES TO CD4 RECEPTOR. CO-RECEPTORS CXCR4 IN T-CELLS AND CCR5 IN MACROPHAGES. gp41 THEN MEDIATES FUSION (NO ENDOCYTOSIS).

REVERSE TRANSCRIPTION - RT FROM VIRUS MAKES cDNA IN CYTOPLASM.

DNA TRANSPORT - VIRAL Vpr PROT TAKES DNA TO NUCLEUS.

DNA INTEGRATION - RANDOMLY INTEGRATED BY (IN)

TRANSACTIVATION - CELLULAR RNA POL II BINDS TO LTR TO MAKE VIRAL RNA.

RNA EXPORT - Rev PROT TAKES RNA TO CYTOPLASM.

TRANSLATION - BLAH, THEN POLYPEPTIDE CLEAVED BY PR.

ASSEMBLY - Vpu REQUIRED TO BRING COMPONENTS TO PM.

BUDDING - BLAH

Vif - INH CELLULAR DEFENCE APPARATUS AGAINST INFECTION

Vpr - TAKES GENOME TO NUCLEUS

Tat - LTR TRANSACTIVATION

Rev - TAKES mRNA FROM NUCLEUS TO CYTOPLASM

Nef - IMMUNE EVASION BY DOWN REGULATING EXPRESSION OF MHC I

Vpu - VIRUS ASSEMBLY

ATTACHMENT TO CELL-SURFACE GLYCOPROTEINS AND FUSION WITH PM

UNCOATING IN CYTOPLASM AND TRANSLOCATION OF GENOME AND PROTS TO NUCLEUS.

DNA CIRCULARIZES, FOLLOWED BY TRANSCRIPTION.

CELLULAR RNA POL II MAKES IMMEDIATE EARLY (IE - ALPHA) GENES --> ALPHA PROTS MADE IN CYTOPLASM.

IE PROTS MOVE TO NUCLEUS TO TRANSACTIVATE EARLY (BETA) mRNA --> PROTS.

INTRACELLULAR MOVEMENT OF VIRAL PROTS BASED ON THEIR STRUCTURE/FUNCTION.

VIRAL DNA MAKES COPIES OF GENOME IN NUCLEUS.

CELLULAR RNA POL II MAKES LATE (GAMMA) mRNA.

REPLICATED DNA CLEAVED TO GENOME LENGTH FOR CAPSID. NUCLEAR BUDDING AFTER NUCLEOCAPSID, TEGUMENT, AND ENV ACQUIRED.

ENV PARTICLES MAY UNDERGO DE-ENV RE-ENV STEPS BEFORE BUDDING.

BUDDING

NON-ENV LINEAR dsDNA

ENTRY - VIA ENDOSOME. CLATHRIN COATED VESICLES. VIRAL FIBER AND PENTON PROTS BIND WITH CELLULAR CAR & INTEGRINS.

RELEASE - ACIDIFICATION CAUSES PATIAL LOSS OF CAPSID STRUCT. MOVES TO NUCLEUS VIA MICROTUBULES & DNA RELEASED INTO NUC.

IMMEDIATE EARLY PROTS - CELLULAR RNA POL II MAKES IE E1A mRNA --> E1A PROTS MADE IN CYTO THEN MOVED TO NUC.

EARLY PROTS - IN NUC, E1A PROMOTES EXPRESSION OF EARLY PROTS WHICH TOGETHER PROMOTE DNA REPLICATION.

LATE PROTS - E1A AND EARLY PROTS PROMOTE EXPRESSION OF LATE PROTS FOR CAPSID.

ASSEMBLY - DNA INSERTED INTO CAPSID.

RELEASE - LYSIS

PICORNA (+)ssRNA; NON-ENV; ICOSA

URT

ENDOCYTOSIS; LYSIS

VP1,2,3 ATTACH TO ICAM1

100+ SEROTYPES

NO VIREMIA

COMMON COLD; CROUP

WINTER

ORTHOMYXO

(-)ssRNA; 8 SEGS;ENV; HELICAL

REPLICATES IN NUC

SIALIC ACID RECEPTORS

ANI & HUM RESIVOIRS (SHIFT & DRIFT)

HA & N; NO F

NO VIREMIA

AVEOLAR EDEMA, PNEUMONIA

FEVER - IL-1 AND TNF-a

ORTHOMYXO

(-)ssRNA; 7 SEGS; ENV; HELICAL

DRIFT; NO SHIFT

INFLUENZA

BLOCKS FLUVA M2

INFLUENZA

BLOCKS FLUVA AND FLUVB N

BLOCKS CLEAVAGE OF SIALIC ACID SO VIRIONS CANNOT ESCAPE

PARAMYXO

(-)ssRNA; ENV; HELICAL

HA & F; NO N

VIREMIA; KOPLIK SPOTS; MACULOPAPULAR RASH (ENDOTHEL CELL KILLING)

GIANT CELLS

SUB-SCLEROSING PANENCEPHALITIS (CMI ON NEURONS)

BLOCKS IFN INDUCED JAK/STAT

PRIMARY MUCOSA --> SECONDARY LYMPH

PARAMYXO

(-)ssRNA; ENV; HELICAL

F ONLY

MOST COMMON INFANT/CHILD VIRAL INFECTION

NO VIREMIA

TREAT RSV - BLOCK F PROTEIN

FOR HIGH-RISK INFANTS, GIVE AERO RIBAVIRIN

FLUORESCENT Ab

PARAMYXO

(-)ssRNA; ENV; HELICAL

HA, N, F

4 SEROTYPES: 1-3 PATHOGENIC

URT IN ADULTS

U/LRT IN KIDS: CROUP; TYPE 3 CAUSES SEVERE LRT & PULMONARY DISTRESS SYNDROME

NO VIREMIA

PARAMYXO

(-)ssRNA; ENV; HELICAL

HA, N, F

PARATITIS; ORCHITIS

VIREMIA

ASEPTIC MENINGITIS, MYOCARDITIS

PICORNA - ENTERO

(+)ssRNA; NON-ENV; ICOSA

FECAL-ORAL; LYSIS; CPE

LYMPH AND NERVOUS SYSTEM (MOTOR)

ABORTIVE, NON-PATALYTIC, PARALYTIC

VACCINES:

eINTRAMUSCULAR - INACTIVATED, 3 SEROTYPES. NO IgA SO POOR GUT PROTECTION

CALICI - ENTERO

(+)ssRNA; NON-ENV; ICOSA

90% OF EPIDEMIC NON-BAC GASTROENTERITIS

FECAL-ORAL; CRUISE, NURSING

>5 SEROTYPES; II MOST COMMON

SAPOVIRUS ANOTHER CALICI

REO - ENTERO

dsRNA; 11 SEGS, NON-ENV; DOUBLE-LAYERED CAPSID

ENTRY THROUGH b-ADREN RECEPTORS

6 SEROTYPES ABCDEF (A IN WINTER); LYSIS

HA USED AS Ab

MAJOR GI INFECTION IN INFANTS & CHILDREN

DUAD TIPS - DEHYDRATION

NSP₄ - ENTEROTOXIN

ROTA-TEQ LIVE ORAL AGAINST 5 SEROTYPES

ROTA-SHIELD -- LIVE VACCINE

DETECTION IN STOOL; ELISA

ADENO 40 & 41: dsDNA; NON-ENV; ICOSO

ASTRO: (+)ssRNA; NON-ENV; SIMILAR TO PICORNA AND CALICI

ENT 70 - ACUTE HEM CONJUNCTIVITIS

ENT 71 - MENINGITIS AND ENCEPH

ENT 72 - SAME AS HEP A (PICORNA - (+)ssRNA, NON-ENV, ICOSO)

PICORNA - ENTERO

(+)ssRNA; NON-ENV; ICOSO

30+ SEROTYPES

• GROUP A - HERPANGIA, ACUTE HEMORRHAGIC CONJUNCTIVITIS,
• HAND-FOOT-AND-MOUTH

• -GROUP B - PLEURODYNIA, MYOCARDITIS,
• CONGESTIVE HEART FAILURE, AND PERICARDITIS (AFFECTS LIVER, HEART, PLEURA, PANCREAS)

-BOTH GROUPS CAUSE URT DISEASE, FEBRILE RASHES, ASEPTIC MENINGITIS

ALANINE TRANSAMINASE (ALT) - HEPATOCYTE ENZ PRESENT IN LIVER DAMAGE

ASP TRANSAMINASE (AST) - ACUTE LIVER DAMAGE BUT LOCATED IN OTHER TISSUES SO NOT SPECIFIC TO LIVER

ALANINE PHOS (ALP) - ALL TISSUES BUT CONC IN LIVER, USED TO DETECT BILE DUCT OBSTRUCTION, etc

GAMMA GLUT TRANS (GGT) - RECENT ALC ABUSE, MINOR LIVER DYSFUNCTION

PICORNA (+)ssRNA NON-ENV

-ONE SEROTYPE

-TRANSMITTED VIA FECAL-ORAL ROUTE

-HUMANS ARE ONLY RESERVOIR

APPEARS IN FECES 2 WEEKS BEFORE SYMPTOMS

• -CHILDREN MOST FREQUENTLY
• INFECTED (SUMMER CAMPS, BOARDING SCHOOL…)

-RARELY TRANSMITTED VIA BLOOD BECAUSE VIREMIA IS LOW AND NO CHRONIC INFECTION

-DIAGNOSE W/ IgM AB TITER; CAN ALSO ISOLATE THE VIRUS IN CELL CULTURE

-NO ANTI-VIRAL THERAPY; ACTIVE IMMUNIZATION W/ VACCINE CONTAINING INACTIVATED HAV IS AVAILABLE

-OR PASSIVE IMMUNIZATION: IMMUNE SERUM GLOBULIN CAN BE GIVEN WITHIN 14 DAYS OF EXPOSURE

HEPADINOVIRUS

PARTIALLY dsDNA; ENV; ICOSA

MANY ASYMPTOMATIC, BUT ONCE ACTIVE MORE SEVERE THAT HEP A

• -CONTAINS DNA-DEPENDENT DNA POLYMERASE; SYNTHESIZES MISSING
• PORTION OF DNA

DANE PARTICLES

• SOME DNA INTEGRATES INTO HOST
• GENOME

-REPLICATION OCCURS IN NUCLEUS

-CELLS RELEASED BY BUDDING

-4 GENES: POL, ENV, PRE-CORE, AND X

• -MALIGNANCY: HIGH INCIDENCE OF
• HEPATOCELLULAR CARCINOMA (HEPATOMA)

• -PRODUCES VIRIONS, SPHERES, AND
• FILAMENTS (EMPTY ENVELOPES)

• -CORE ANTIGEN FORMS CAPSID CORE OF
• VIRION, E ANTIGEN IS SECRETED FROM INFECTED CELLS INTO BLOOD (INDICATOR OF TRANSMISSIBILITY)

• -TRANSMITTED VIA BLOOD, SEX, AND
• PREGNANCY

• -ONE SEROTYPE (BASED ON HBSAG)
• REGARDING VACCINES; 4 SEROTYPES EPIDEMIOLOGICALLY

-CYTOTOXIC T CELLS

• -HUMANS ARE ONLY RESERVOIR;
• PARTICULARLY PROMINENT IN ASIA

• -ABOUT 5% INFECTED BECOME CHRONIC
• CARRIERS

FLAVIVIRUS

(+)ssRNA; ENV;

6 SEROTYPES "C FOR CHYMERA"; HIGH MUTATION RATE

LESS SEVERE THAN HEP B BUT MORE CHRONIC

LIVER DAMAGE BY CYTOTOXIC T CELLS

BLOOD; SEX

• BLOCKS p53 "C FOR CANCER"

• -DIAGNOSED BY DETECTING AB IN ELISA
• (Ag IN ASSAY IS A RECOMBINANT PROTEIN FORMED FROM THREE IMMUNOLOGICALLY STABLE HCV PROTEINS AND DOES NOT INCLUDE HIGHLY VARIABLE ENVELOPE PROTEINS)

• B/C FALSE + CAN OCCUR, RIBA SHOULD
• BE PERFORMED AS A CONFIRMATORY TEST

• -TREATMENT OF ACUTE HEP C WITH
• ALPHA INTERFERON DECREASES THE # OF PTS THAT BECOME CHRONIC CARRIERS

• -TREATMENT FOR CHRONIC CARRIERS IS
• COMBINATION OF PEGINTERFEREON (PEGASYS) AND RIBAVIRIN

DELTA VIRUS

Enveloped, (-) ssRNA, covalently closed circle

-SIMILAR TO HBV

-HDV AND HBV WORSE BUT CHRONIC HEP IS ABOUT THE SAME

- DEFECTIVE VIRUS (CANNOT REPLICATE BY ITSELF BECAUSE IT DOES NOT HAVE ANY GENES FOR ENVELOPE PROTEIN)

-GENOME ENCODES ONLY ONE PROTEIN, INTERNAL CORE PROTEIN CALLED DELTA ANTIGEN

-RNA IS RIBOZYME; HAS ABILITY TO SELF-CLEAVE AND SELF-LIGATE

-REPLICATION IN NUCLEUS

-ONE SEROTYPE (LIKE HBV)

-HUMANS ONLY RESERVOIR

-TRANSMITTED SAME AS HBV (BLOOD, SEX, PREGNANCY); PATHOGENESIS SAME AS HBV; DELTA ANTIGEN MAY BE CYTOPATHIC FOR HEPATOCYTES

-IMMUNITY UNCERTAIN BECAUSE IgG AGAINST DELTA Ag NOT DETECTED FOR LONG PERIODS AFTER INFECTION

VACCINE

ADEFOVIR

a-INF

LAMIVUDINE

LINEAR dsDNA

FIBER AND PENTON BIND TO INTEGRINS

41 SEROTYPES

NUC ALONG MICROTUBULES

CAUSE PERSISTANT INFECTION

HOST RNA POL II --> E1A --> ACTIVATES EARLY & CELL GENES TO READY FOR REPLICATION --> E2 HAS VIRAL DNA POL FOR REP

E1A DELAYED EARLY AND LATE GENES L1-L5 FOR STRUCT PROTS (ALSO p53 AND Rb) --> SELF ASSEMB IN NUC --> HOST PROT SYNTH SHUT OFF --> LYSIS

E1B AND E3 BLOCK CTL MED APOP AND MHC I

LATENT INFECT GI & LYMPH

3,4,7,21 LRT PNEMONIA OR ACUTE RESP DISEASE (ARD) IN KIDS & OVERCROWDED FATIGUED POPS

11,21 --> ACUTE HEM CYSTITIS, VIREMIA HEMATURIA NO FEVER MAINLY BOYS (KIDNEY)

40,41 --> GI

8,19 --> CONJUNCTIVITIS; EPIDEMIC KERATO-CONJUNCT

SHELL VIAL ASSAY

cdsDNA; NON-ENV; HISTONES; CAP PROT L1

>100 SEROTYPES

16,18,31,45 --> CERVICAL CARCINOMA

1. ATTACHES TO INTEGRINS, ENDOCYTOSIS

2. UNCOATING BY ACIDIFICATION

3. REPLICATION IN NUC VIA CELL’S DNA POLY AND RNA POL

5. E4 DISRUPTS CYTOKERATINS TO ALLOW EXIT DURING KOILOCYTOSIS (LYSIS?)

• 1. INFECTS EPIDERMAL CELLS AND
• CAUSES KOILOCYTES

GEN-URO CONDYLOMAS IMPEDE

2. INFECT BASAL LAYER BUT NO VIRUS MADE; MADE IN SUPERFICIAL LAYER

3. SKIN-TO-SKIN CONTACT OR GENITAL CONTACT

4. NO VIREMIA

3. E6 INACTIVATE P53 AND E7 INACTIVATES POCKET PROTEINS PRB, P107, AND P130 DRIVES CELLS TO S PHASE

1. BOTH CMI AND Ab ARE INDUCED BY VIRAL INFECTION

2. DNA HYBRIDIZATION TESTS TO DETECT PRESENCE OF VIRAL DNA

1. DESTROY WARTS WITH CHEMICALS (PODOPHYLLIN), CRYOSURGERY, LASER, ELECTRO

2. a-IFN (GOOD AT PREVENTING RECURRING INFECTIONS)

3. IMMUNE RESPONSE MODULATORS (IMIQUIMOD)

3. GARDASIL VACCINE (APPROVED FOR WOMEN 9-26)-CONTAINS L1 CAPSID PROTEINS FOR TYPES 6,11,16,18

4. CERVARVIX-L1 AGAINST 16,18,31,45

2. SKIN WARTS-TYPES 1-4

3. GENITAL WARTS-TYPES 6 AND 11 (30 TYPES INFECT GENITAL TRACT)

cdsDNA; NON-ENV; HISTONES; ICOSA

1. ADSORPTION TO GLYCOPROTEINS (ASTROCYTES/OLIGODENDROCYTES IN JC, KIDNEY IN BK)

2. UNCOATING AS GENOME IS INJECTED INTO NUCLEUS

3. REPLICATION IN NUC

4. ASSEMBLY IN CYTO THEN NUC

5. RELEASE BY VESICULAR EXOCYTOSIS

1. INFECT MUCOSAL EPI AND SPREADS BY VIREMIA TO TARGET TISSUES

2. TRANSMISSION-RESPIRATORY

4. NATURAL HOST IS MOUSE

2. INTEGRATES INTO CELL DNA AND ONLY EARLY PROTEINS ARE MADE, INCLUDING T Ag (REQUIRED FOR MAINTENANCE OF TRANSFORMED STATE)

3. LYTIC/PERSISTENT

4. OFTEN MILD OR ASYMPTOMATIC; POSSIBILITY OF LIFE-LONG INFECTIONS OF CARRIERS WHO SHED VIRUS IN URINE

5. BK CAUSES KIDNEY CYSTITIS, NEPHRITIS, AND KIDNEY ALLOGRAFT FAILURE

JC PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-DUE TO OLIGODENDROCYTE AND ASTROCYTE DESTRUCTION (CAN INFECT B CELLS ALSO)

INFLAMMATION CAN RESULT IN PLAQUES OF DEMYELINATION

HEMIPARESIS, DEMENTIA, VISUAL SENSORY FXN LOSS; MOST PATIENTS DIE WITHIN 6 MONTHS (DISEASE OCCURS WHEN LATENT JC VIRUS IS ACTIVATED IN AN IMMUNO-COMPROMISED PATIENT)

SV40 VIRUS CAUSES MALIGNANT TUMORS IN NON-HUMAN SPECIES SUCH AS HAMSTERS

DEFENSES: SERUM Ab, CMI

DIAGNOSIS

1. SX TRIAD

2. CNS LESIONS ON CT/MRI

3. IMMUNO-STAINING, PCR

4. HA INHIBITION

TREATMENT:

1. PML TX WITH IFN-ALPHA, CIDOFOVIR, ARA-C, HAART, AZT

1.NO VACCINE

1. JCV NOT A PROBLEM FOR HEALTHY PPL

• 2. INFECTIONS
• ARE COMMON WORLDWIDE

3. OCCUR IN EARLY CHILDHOOD

VIRUS PERSISTS IN KIDNEY, TONSILS, LYMPHOCYTES

RETROVIRUS

2. 2 ssRNA GENOMES

3. ENV HELICAL; gp21 AND gp46 SURFACE PROTEINS

VIRUS BINDS TO CD4 T CELLS OR DEND CELLS, FUSING WITH CELL MEMBRANE

VIRION UNCOATING ACTIVATES REVERSE TRANSCRIPTASE (RT) TO MAKE CDNA

cDNA TRAVELS TO NUC, WAITS FOR MITOSIS, INTEGRATES INTO HOST GENOME

HOST RNA POL II

TL IN CYTOPLASM

ASSEMBLY IN CYTOPLASM; BUDDING

1. INFECTS T CELLS OR DENDRITIC CELLS (LYMPHOID TISSUE), TRAVELS THROUGH BLOOD TO OTHER TISSUES

SEXUAL CONTACT AND BLOOD

TRANSFEROF ENTIRE INFECTED CELLS!!!!

HAM/TSP

INFECTS SPINAL CORD T-CELLS, CAUSE SPASTIC GAIT AND BLADDER DYSFUNC.

EXCLUDE MS; TEST CSF

HTLV INFECTS T CELLS BUT DOES NOT KILL THEM; IMMORTALIZES THEM BY MALIGNANT TRANSFORMATION

ATL

TAX ACTIVATES IL-2 AND IL-2 RECEPTOR WHICH CAUSES RAPID T-CELL GROWTH AND EVENTUAL MALIGNANT

STIMULATES ONCOGENESIS

USUALLY MONOCLONAL

• SX OF LYMPHADENOPATHY, HEPATOSPLENOMEGALY, LYTIC BONE LESIONS, AND SKIN LESIONS
• (PROLIFERATING T CELLS INFILTRATING THESE ORGANS-T CELLS HAVE DISTINCTIVE FLOWER-SHAPED NUCLEI)

HYPERCALCEMIA DUE TO INCREASED OSTEOCLAST ACTIVITY

REDUCED CMI, OPPORTUNISTIC INFECTIONS

HTLV-ASSOCIATED PROGRESSIVE MYELOPATHY

DEMYELINATING DISEASE OF BRAIN AND SPINAL CORD, MOTOR NEURONS IN SPINAL CORD; CD8 T CELLS DIRECTED AGAINST HTLV Ag ACCUMULATE IN CSF

EITHER CAUSED BY AUTOIMMUNE CROSS-REACTION IN WHICH THE IMMUNE RESPONSE AGAINST HTLV DAMAGES NEURONS, OR BY CTL ATTACK OF HTLV-INFECTED NEURONS

SX (AFTER AGE 30) OF GAIT DISTURBANCE, WEAKNESS OF LOWER LIMBS; LOSS OF BOWEL AND BLADDER CONTROL (BLADDER SX OF URINARY FREQUENCY, URGENCY, INCONTINENCE, ETC) *LOSS OF MOTOR FUNCTION MUCH GREATER THAN SENSORY LOSS

• PARAPARESIS MAY INITIALLY BE ASYMMETRICAL BUT EVENTUALLY PROGRESSES TO SYMMETRICAL SPASTIC
• GAIT

BACK PAIN, CONSTIPATION, SEXUAL DYSFXN COMMON

• PTS MAY ALSO HAVE UVEITIS, ARTHRITIS,
• POLYMYOSITIS, KERATOCONJUNCTIVITIS SICCA (DRYNESS OF CORNEA AND CONJUNCTIVA), AND INFECTIOUS DERMATITIS

• v.
• PRINCIPLE HOST DEFENSE

• 1.
• Ab AGAINST HTLV

CD8 T CELLS

DIAGNOSIS: Ab AGAINST VIRUS IN ELISA (WESTERN BLOT TO CONFIRM)

PCR FOR HTLV RNA OR DNA WITHIN INFECTED CELLS

ATL DIAGNOSED BY FINDING MALIGNANT T CELLS IN LESIONS

HAM DIAGNOSED BY PRESENCE OF Ab IN CSF

NO ANTIVIRAL THERAPY

ATL TREATED WITH ANTICANCER CHEMO

HAM-CORTICOSTEROID AND DANAZOL PROVIDES SOME HELP

NO VACCINE

SCREENING DONATED BLOOD

CONDOMS

NO BREAST FEEDING FOR WOMEN WITH HTLV AB’S

INTERESTING FACTS ABOUT VIRUS

• STRUCTURE: *GAG (STRUCTURAL PROTEINS), *POL (REVERSE TRANSCRIPTASE, INTEGRASE, PROTEASE), *ENV (ENVELOPE PROTEINS), PLUS TWO REGULATORY GENES TAX (TC
• ACTIVATOR SIMILAR TO TAT OF HIV) AND REX (GOVERNS PROCESSING OF VIRAL MRNA AND ITS EXPORT FROM NUCLEUS TO CYTOPLASM)

• DIFFERENCES BETWEEN HIV AND HTLV-DIFFERENT REGULATORY GENES, DIFFERENT p24 NUCLEOCAPSID PROTEIN (IMPORTANT PROTEIN BECAUSE
• THIS IS THE ONE THAT MANY AB’S ARE MADE AGAINST), AND DIFFERENT SURFACE
• PROTEINS (GP21/46 FOR HTLV, GP120/41 FOR HIV)

• 1. RETROVIRUS-LENTIVIRUS
• GROUP (SLOW INFECTIONS WITH LONG INCUBATION PERIODS)

2. 2 ssRNA; ENV HELICAL CAPSID WITH GP120 AND GP41 SURFACE PROTEINS

1. GP120 ATTACHES TO CD4 RECEPTOR ON T CELLS (CCR5 ON MACROPHAGES AND CXCR4 ON T CELLS ACT AS CO-RECEPTORS)

2. GP41 MEDIATES FUSION OF THE VIRAL ENVELOPE WITH THE PM

3. VIRAL GENOME DELIVERED INTO CYTOPLASM UPON UNCOATING

4. RNA TO CDNA BY RT IN CYTO

5. cDNA TRANSPORTED TO NUC (VIA Vpr) AND INTEGRATED INTO HOST GENOME (VIA INTEGRASE)

6. CELLULAR RNA POL II INTERACTS WITH LTR (Tat) TO TC GENOME INTO VIRAL MRNA

7. mRNA TRANSPORTED TO CYTO TO BE TL INTO PROTS (VIA Rev)

8. PROTS CLEAVED INTO FINAL FRAGMENTS BY VIRAL PROTEASE

9. ASSEMBLY ON PM (NEED Vpu)

10. BUDDING

ROUTE OF INFECTION

1. TRAUMATIZED MUCOUS MEMBRANE THAT ALLOWS GP120 OF HIV TO INTERACT WITH DC-SIGN OF DEND CELLS

• 2. DEND CELLS TRAVEL TO LNs à
• CD4 T CELLS

3. INFECTED BLOOD, SEXUAL CONTACT, PERINATAL

SYMPTOMS AND HALLMARKS OF DISEASE

1. PROVIRUSES MIGRATE TO LYMPHOID TISSUES WHERE THEY CAN REMAIN LATENT

2. VIRUS ABLE TO EVADE HOST DEFENSE

a. INTEGRATION INTO HOST GENOME

b. Tat AND Nef PROTS DOWN-REGULATE MHC CLASS I EXPRESSION

c. HIGH MUTATION OF ENV GENE (Ag VARIATION)

3. INITIAL VIREMIA HIGH-SETS VIRAL LOAD (DETERMINES LIKELIHOOD OF PROGRESSION TO FULL-BLOWN AIDS)

4. ALSO TARGETS CD4 TH17 CELLS-LEADING TO LOSS OF MUCOSAL IMMUNITY AND INCREASED SUSCEPTIBILITY TO BLOOD STREAM INFECTIONS BY BACTERIA IN NORMAL FLORA (E COLI)

• 5. VIRUS ALSO TARGETS BRAIN MONOCYTES AND MACROPHAGES-FORM OF MULTI-NUCLEATED GIANT
• CELLS THAT CAUSE CNS SX

6. HIV INFECTION DIVIDED INTO 3 STAGES:

a. ACUTE STAGE-BEGINS 2-4 WKS AFTER INFECTION; A MONO-TYPE PICTURE OF FEVER, LETHARGY, SORE THROAT, AND GENERALIZED LYMPHADENOPATHY (MAY SEE MACULOPAPULAR RASH ON TRUNK, ARMS, LEGS)

LEUKOPENIA OCCURS

HIGH VIREMIA

INFECTION IS READILY TRANSMISSIBLE

RESOLVES SPONTANEOUSLY IN ABOUT 2 WKS BY ACTION OF CD8 T CELLS

Ab APPEARS ABOUT 10-14 DAYS AFTER INFECTION

b. MIDDLE STAGE

LONG LATENT INFECTION, LASTING FOR YEARS

PT IS ASYMPTOMATIC AND VIREMIA LOW; HOWEVER, VIRUS ITSELF IS NOT LATENT, BECAUSE VIRUS IS MAKING MORE OF ITSELF AND STAYING SEQUESTERED IN LN’S

CAN SEE AIDS-RELATED COMPLEX-PERSISENT FEVERS, FATIGUE, WEIGHT LOSS, AND LYMPHADENOPATHY (USUALLY PROGRESSES TO AIDS)

c. LATE STAGE-AIDS

CD4 T CELL COUNT BELOW 400 (CAN USE THIS TO TRACK INFECTION)

INCREASE IN FREQUENCY AND SEVERITY OF OPPORTUNISTIC INFECTION, MOST COMMON OF WHICH ARE PNEUMOCYSTIS PNEUMONIA AND KAPOSI’S SARCOMA

PRINCIPLE HOST DEFENSE

1. INNATE IMMUNITY

2. CD8 T CELL ATTACK

ALPHA-DEFENSINS (BLOCK BINDING TO CXCR4 RECEPTOR)

DIAGNOSIS

1. DETECTION OF AB IN ELISA (GIVES MANY FALSE-POSITIVES SO DO A WESTERN BLOT TO CONFIRM; AB AGAINST P24, GP41)

2. ORAQUICK-BLOOD SAMPLE OBTAINED BY FINGERPRICK; RAPID IMMUNOASSAY FOR HIV AB AVAILABLE IN 20 MIN

3. PCR TO DETECT HIV DNA

TREATMENT

• 1. HAART-EITHER 2 NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (LIKE LAMIVUDINE, ZIDOVUDINE) AND
• ONE PROTEASE INHIBITOR (FOSAMPRENAVIR) OR 2 NRTI’S AND ONE NON-NUCLEOSIDE RT INHIBITOR (EFAVIRENZ)

PREVENTION

1. NO VACCINE

2. CONDOMS, SCREEN DONATED BLOOD, NO SHARING NEEDLES

3. ZDV OR NEVIRAPINE GIVEN PERINATALLY TO INFECTED MOMS AND NEONATES; NO BREAST FEEDING; C-SECTION

INTERESTING FACTS ABOUT VIRUS

1. STRUCTURE OF GENOME-GAG, POL, ENV, VPR, VPU, REV, TAT, VIF (INHIBITING ACTION OF ENZYME THAT CAUSES HYPERMUTATION IN RETROVIRAL DNA AND INACTIVATES IT) , NEF

• 2. TYPES-HIV 1 (FROM CHIMP) CAUSES MOST AIDS CASES AND IS FURTHER CLASSIFIED INTO SUBTYPES/CLADES (GOOD FOR STUDYING REGIONAL PATTERNS), HIV 2 (FROM SOOTY
• MANGABEY)

KAPOSI’S SARCOMA

1. CAUSED BY HERPES VIRUS

2. ONE OF THE MOST COMMON OPPORTUNISTIC INFECTIONS SEEN IN AIDS PATIENTS

3. PRIMARY INFECTION LIKELY TO BE FEBRILE ILLNESS

• 4. MAINLY INFECTS B CELLS AND VASCULAR ENDOTHELIAL CELLS (AB AND CMI DEVELOP AND RESTRICT
• LATENT AND LYTIC INFECTIONS BUT CAN’T CLEAR VIRUS)

5. 3 TYPES:

a. CLASSIC KS (ELDERLY MEDITERRANEAN MALES)

b. ENDEMIC KS (CENTRAL AFRICAN CHILDREN)

c. AIDS-ASSOCIATED KS

• ENDOTHELIAL CELL TUMOR-CELLS ARE TRANSFORMED DUE TO INACTIVATION OF P53 AND POCKET PROTEINS; ALSO PRODUCTION OF KAPOSINS THAT ACTIVATE SIGNALING PATHWAYS TO
• STIMULATE CELL GROWTH

ALSO MAY ENCODE ANTI-APOPTOTIC PROTEINS THAT RESIST CTL KILLING

CAUSE CHARACTERISTIC PURPLE SKIN LESIONS

DIAGNOSIS BY OBSERVATION, BIOPSY; ELISA, WESTERN BLOT, IMMUNOFLUORESCENCE TO DETECT AB TO KSHV PROTEINS

TX WITH HAART, REMOVE LESIONS BY SURGERY, RADIATION, IFN, OR VINBLASTINE

1. HERPES VIRUS -ALPHA GROUP

2. LINEAR dsDNA GENOME

• 3. ENVELOPED
• ICOSAHEDRAL CAPSID

LIFE CYCLE

1. BINDS TO HEPARAN SULFATE ON CELL MEMBRANE AS RECEPTOR AND BINDS TO 2ND RECEPTOR, NECTIN

• 2. VIRION ENVELOPE FUSES WITH PLASMA MEMBRANE AND RELEASES GENOME + TEGUMENT PROTEIN INTO
• CYTO

3. GENOME DNA AND TEGUMENT PROTEIN (VP16) GET INTO NUCLEUS BY DOCKING TO NUCLEAR PORE

4. LINEAR dsDNA BECOMES CIRCULAR; VP16 INTERACTS WITH TC FACTORS TO INITIATE TC OF IE GENES OF DNA

5. TL OF IE PROTEINS (NON-STRUCTURAL PROTEINS) IN CYTO

6. ACTIVATION OF TC AND TL OF E PROTEINS (DNA POL AND THYMIDINE KINASE)

7. VIRAL DNA POL REPLICATES GENOME DNA

8. TC AND TL OF L PROTEINS (STRUCTURAL PROTEINS)-TO NUCLEUS

9. ASSEMBLY IN NUCLEUS

10. BUDDING FROM NUCLEAR MEMBRANE AND EXIT BY TUBULES AND VACUOLES

ROUTE OF INFECTION

1. HSV REPLICATES IN EPITHELIAL CELLS, ACCESSES NERVE ENDINGS, AND IS TRANSPORTED RETROGRADE TO NEURON NUCLEI

2. HSV-1=TRANSMITTED BY SALIVA

MOST COMMON USA CAUSE OF ENCEPHALITIS

3. HSV-2=TRANSMITTED BY SEXUAL CONTACT

4. BOTH HAVE ASYMPTOMATIC SHEDDING

SYMPTOMS AND HALLMARKS OF DISEASE

1. PRIMARY INFECTION PUTS VIRUS IN SENSORY GANGLIA (TRIGEMINAL IN HSV-1 AND LUMBAR AND SACRAL GANGLIA IN HSV-2); INFECTION ACTIVATES A POTENT IMMUNE RESPONSE THAT RESTRICTS SPREAD AND RESOLVES SX (VIRUS NOT GONE)

2. LATENT INFECTION:

a. HSV PERSISTS AS CIRCULAR DNA IN NUCLEUS (NOT INTEGRATED INTO GENOME)

b. TC LAT’S (LATENCY ASSOCIATED TRANSCRIPTS) THAT BLOCK VIRAL REPLICATION

c. IMMUNE EVASION BY NEURONS THAT ARE BEHIND THE BLOOD-BRAIN BARRIER, EXPRESS LOW LEVELS OF MHC AND DIVIDE INFREQUENTLY

• 3. REACTIVATION: LYTIC INFECTION INDUCED BY UV EXPOSURE, STRESS, HORMONE CHANGES, ETC. (ENABLES
• SHEDDING FROM EPI CELLS)

4. HSV-1

a. 2-12 DAY INCUBATION PERIOD THEN PRESENT WITH FEVER, PHARYNGITIS, MALAISE, EDEMA, ETC. (SKIN LESIONS USUALLY RESOLVE)

• b. GINGIVOSTOMATOSIS-PRIMARILY
• IN KIDS; FEVER, IRRITABILITY, VESICULAR LESIONS IN MOUTH (RESOLVE IN 2-3 WKS)

• c. HERPES LABIALIS (COLD SORE)-MILDER, RECURRENT FORM WITH CROPS OF LESIONS AT MUCOCUTANEOUS
• JXN OF LIPS OR NOSE

• d. KERATOCONJUNCTIVITIS-CORNEAL
• ULCERS AND LESIONS OF CONJUNCTIVIAL EPI (RECURRENCES-SCARRING, BLINDNESS)

e. ENCEPHALITIS

NECROTIC LESION IN ONE TEMPORAL LOBE

FEVER, HEADACHE, VOMITING, SEIZURES, ALTERED MENTAL STATUS (ACUTE OR PROTRACTED OVER SEVERAL DAYS)

EXAMINATION OF CSF SHOWS MODERATE INCREASE IN LYMPHOCYTES, ELEVATION IN PROTEINS, AND NORMAL GLUCOSE

HIGH MORTALITY RATE AND SEVERE NEUROLOGICAL SEQUELAE IN THOSE WHO SURVIVE

HERPETIC WHITLOW-PUSTULAR LESION OF SKIN OF FINGER OR HAND (MEDICAL PERSONNEL IN CONTACT WITH PATIENT’S LESIONS)

g. HERPES GLADIATORUM-OCCURS IN WRESTLERS OR PPL WITH CLOSE BODY CONTACT; VESICULAR LESIONS ON HEAD, NECK, AND TRUNK

DISSEMINATED INFECTIONS IN IMMUNOCOMPROMISED PATIENTS WITH DEPRESSED T-CELL FXN

LARGE

dsDNA, ENV

TEGUMENT

a. GENITAL HERPES-PAINFUL VESICULAR LESIONS OF MALE AND FEMALE GENITALIA AND ANAL AREA (PRIMARY INFECTION ASSOC. WITH FEVER AND INGUINAL ADENOPATHY)

• b. NEONATAL HERPES-CONTACT WITH VESICULAR LESIONS OF BIRTH CANAL-RANGE FROM SEVERE
• ENCEPHALITIS OR DISSEMINATED LESIONS TO MILDER LOCAL LESIONS OF SKIN,ETC. TO ASYMPTOMATIC INFECTION

c. ASEPTIC MENINGITIS-MILD, SELF-LIMITING

2. BOTH TYPES 1 AND 2 ARE ASSOCIATED WITH ERYTHEMA MUTLIFORME-“TARGET” LESION ON TRUNK, HANDS, AND FEET (THOUGHT TO BE IMMUNE-MEDIATE RXN TO HSV AG)

PRINCIPLE HOST DEFENSE

1. IMMUNITY IS TYPE-SPECIFIC, BUT SOME CROSS-RXN CAN OCCUR

2. IMMUNITY IS INCOMPLETE, IGG

3. CMI MORE IMPORTANT

DIAGNOSIS

1. ISOLATION OF VIRUS FROM LESION BY GROWTH IN CELL CULTURE (VERIFY BY ELISA)

• 2. TZANCK SMEAR-RAPID DX, LOOK FOR
• MULTINUCLEATED GIANT CELLS

3. PCR


4. SEROLOGICAL TESTING FOR PRIMARY INFECTION

TREATMENT

1. ACYCLOVIR-SHORTENS DURATION OF LESION AND REDUCES EXTENT OF SHEDDING

2. FOSCARNET IF RESISTANT TO ACYCLOVIR

3. VALTREX, FAMVIR

4. CAN’T CURE LATENT STATE

PREVENTION

1. AVOIDING CONTACT WITH VESICULAR LESION OR ULCER

2. C-SECTION FOR MOMS AT TERM WITH GENITAL LESIONS OR POSITIVE VIRAL CULTURES

INTERESTING FACTS ABOUT VIRUS

1. HSV MOST COMMON CAUSE OF SPORADIC ENCEPHALITIS

2. PRIMARY INFECTIONS ALWAYS WORSE THAN RECURRENT INFXN

ALPHA - WIDE HOST RANGE, RAPID REPLICATION, NERVOUS SYSTEM. ex HSV-1&2, VARICELLA ZOSTER, CELL DISTRUCTION CPE!

BETA - NARROW HOST RANGE, SLOW REP, IMMUNE SYSTEM. ex CMV, ROSEOLOVIRUS (HHV 6-7)

GAMMA - NARROW HOST RANGE, MOD RAPID REP, IMMUNE SYSTEM AND TUMOR DEV. ex EBV, KSHV

LYTIC

SHUT OFF HOST PROT SYNTH

OWL-EYE

FUSION (SYNCYTIA)

1. HERPES VIRUS FAMILY-GAMMA GROUP

2. LINEAR dsDNA

3. ENVELOPED ICOSAHEDRAL CAPSID

TEGUMENT

MOST COMMON INFECTION WORLDWIDE; 90% ADULTS USA

OWL'S-EYE

LIFE CYCLE SEE HSV

• 1. TRANSMITTED IN SALIVA, LYTIC VIRUS INFECTION OF MUCOSAL EPITHELIUM ENABLES SPREAD IN BLOOD
• OR LYMPH (TO GET TO B CELLS)

2. ESTABLISHES LATENT INFECTION IN B CELLS-DNA IN NUCLEUS AND IS NOT INTEGRATED INTO GENOME

SYMPTOMS AND HALLMARKS OF DISEASE

• 1. CIRCULAR DNA IN THE NUCLEUS EXPRESSES GENE PRODUCTS THAT MAINTAIN/REPLICATE EBV DNA OR
• TRANSFORM THE B CELLS INTO AN INDEFINITELY PROLIFERATING CELLS LINE

2. INFECTIOUS MONONUCLEOSIS

a. PRIMARY DISEASE OF YOUNG ADULTS/ADOLESCENTS ATTRIBUTED TO HIGHER LEVELS OF VIRUS TRANSMISSION DURING INTIMATE ORAL CONTACT

b. SX OF FEVER, LYMPHADENOPATHY, MALAISE, HEADACHE, HETEROPHILE AB, T CELL LYMPHOCYTOSIS, NUCLEAR ATYPICAL T CELLS, RASH (EXACERBATED BY PENICILLIN), ENLARGED LIVER OR SPLEEN, WEIGHT LOSS

c. RECOVER IN WEEKS TO MONTHS IS TYPICAL

3. ORAL HAIRY LEUKOPLAKIA-IN AIDS PATIENTS; LYTIC EBV-INFECTED CELLS ALONG TONGUE (LIKE CANDIDA BUT NOT EASY TO SCRAPE OFF)

4. LYMPHOPROLIFERATIVEDISEASE-NON-HODGKIN’S LYMPHOMA IN IMMUNE SUPPRESSED TRANSPLANT RECIPIENTS AND AIDS PTS. (MALIGNANT CELLS ARE LATENT EBV TRANSFORMED B-CELLS)

PRINCIPLE HOST DEFENSE

1. FIRST IGM AB TO VCA (VIRAL CAPSID ANTIGEN)

2. IgG AB FOLLOWS AND PERSISTS FOR LIFE

3. HETEROPHIL

DIAGNOSIS

1. CLINICAL SYMPTOMS

2. SMEAR-ATYPICAL LYMPHS

3. MONOSPOT ELISA-DETECT HETEROPHIL AB

4. ELISA FOR EBV-SPECIFIC IGM OR IGG

NO ANTIVIRAL THERAPY

2. HIGH-DOSE ACYCLOVIR FOR LIFE-THREATENING INFECTIONS

PREVENTION

1. NO VACCINE

INTERESTING FACTS ABOUT VIRUS

1. CANCERS OF LYMPHOID ORIGIN ASSOCIATED WITH EBV: NASOPHARYNGEAL CARCINOMA (SOUTH CHINA AND SOUTHEAST ASIA), BURKITT’S LYMPHOMA (CHROMOSOME TRANSLOCATION OF IG GENE ENHANCER DRIVING EXPRESSION OF C-MYC PROTO-ONCOGENE); HODGKIN’S LYMPHOMA (MALIGNANT B CELLS; DEFECTIVE INHIBITOR OF NF-KB THAT REGULATES TC)

1. HERPES VIRUS FAMILY-BETA GROUP

2. LINEAR dsDNA, ENV, ICOSA

ROUTE OF INFECTION

1. EARLY IN LIFE-TRANSMITTED ACROSS PLACENTA, WITHIN BIRTH CANAL, AND BREAST MILK

2. CHILDHOOD=SALIVA

3. ADULTS-SEXUAL TRANSMISSION (SEMINAL AND CERVICAL SECRETIONS), BLOOD TRANSFUSIONS, TRANSPLANTS

SYMPTOMS AND HALLMARKS OF DISEASE

1. INFECTION IN CHILDREN AND ADULTS USUALLY ASYMPTOMATIC, EXCEPT IN IMMUNOCOMPROMISED INDIVIDUALS (LATENT STATE IN LEUKOCYTES THAT CAN BE RE-ACTIVATED WHEN CMI IS LOW)

2. INFECTION IN FETUS CAUSE CYTOMEGALIC INCLUSION DISEASE

a. CHARACTERIZED BY MULTINUCLEATED GIANT CELLS WITH PROMINENT INTRANUCLEAR INCLUSIONS (OWL’S EYE INCLUSIONS)

b. AFFECTS MANY ORGANS AND WIDESPREAD CONGENITAL ABNORMALITIES RESULT-DURING MOM’S PRIMARY INFECTION AND WORSE IF DURING 1ST TRIMESTER

c. SX OF MICROCEPHALY, SEIZURES, DEAFNESS, JAUNDICE, AND PURPURA, HEPATOSPLENOMEGALY, MR

3. HETEROPHIL-NEGATIVE MONONUCLEOSIS IN IMMUNOCOMPETENT ADULTS-FEVER, LETHARGY, PRESENCE OF ABNORMAL LYMPHOCYTES IN BLOOD SMEAR

4. SYSTEMIC CMV INFECTIONS, ESPECIALLY PNEUMONITIS, HEPATITIS, RETINITIS IN IMMUNOSUPPRESSED PATIENTS (AIDS, TRANSPLANT RECIPIENTS)

PRINCIPLE HOST DEFENSE

1. CIRCULATING AB AND CMI

DIAGNOSIS

1. SHELL VIAL ASSAY (CULTURE VIRUS) COUPLED WITH USE OF IMMUNOFLUORESCENT AB

2. FLUORESCENT AB AND HISTOLOGICAL STAINING OF INCLUSION BODIES-OWL’S EYE SHAPE

3. PP65 AG DETECTION WITHIN BLOOD LEUKOCYTES USING IMMUNOFLUORESCENCE ASSAY

1. GANCICLOVIR, VALGANCICLOVIR, FOSCARNET, CIDOFOVIR, FOMIVIRSEN

PREVENTION

1. NO VACCINE

2. ISOLATION OF INFECTED INFANTS

3. ONLY CMV-NEGATIVE TRANSPLANT DONORS AND BLOOD DONORS

• HIGH TITER IMMUNE GLOBULIN (CYTOGAM) TO PREVENT DISSEMINATED
• CMV INFECTION IN TRANSPLANT RECIPIENTS

1. HERPES VIRUS-ALPHA GROUP

2. LINEAR dsDNA, ENV, ICOSA

ROUTE OF INFECTION

1. TRANSMITTED BY RESPIRATORY DROPLETS AND BY DIRECT CONTACT WITH LESIONS

2. VARICELLA-PRIMARY DISEASE; ZOSTER/SHINGLES IS RECURRENT FORM

SYMPTOMS AND HALLMARKS OF DISEASE

1. VZV INFECTS MUCOSA OF URT THEN SPREADS VIA BLOOD TO SKIN, WHERE TYPICAL VESICULAR RASH OCCURS

2. MULTI-NUCLEATED GIANT CELLS WITH INTRANUCLEAR INCLUSIONS ARE AT BASE OF LESIONS

3. VIRUS INFECTS SENSORY NEURONS AND IS CARRIED BY RETROGRADE FLOW TO DORSAL ROOT GANGLIA WHERE VIRUS BECOMES LATENT

• 4. LATENTLY INFECTED CELLS-DNA IN NUCLEUS AND NOT INTEGRATED INTO GENOME; LATER IN TIMES OF REDUCED CMI OR TRAUMA, VIRUS IS REACTIVATED TO VESICULAR RASH AND NERVE PAIN OF
• ZOSTER

5. VARICELLA

a. INCUBATION PERIOD 2-12 DAYS

b. BRIEF PRODROMAL SX OF FEVER AND MALAISE

c. PAPULOVESICULAR RASH APPEARS ON TRUNK AND SPREADS TO HEAD AND EXTREMITIES; ITCHING

d. MILD IN CHILDREN AND SEVERE IN ADULTS

e. POSSIBILITY OF REYE’S SYNDROME WITH ASPIRIN

6. ZOSTER

a. OCCURRENCE OF PAINFUL VESICLES ALONG THE COURSE OF A SENSORY NERVE OF HEAD OR TRUNK

b. PAIN CAN LAST FOR WEEKS AND POSTZOSTER NEURALGIA CAN BE DEBILITATING

c. LIFE-THREATENING DISSEMINATED INFECTIONS LIKE PNEUMONIA CAN OCCUR IN IMMUNOCOMPROMISED PATIENTS

PRINCIPLE HOST DEFENSE

1. IMMUNITY FOLLOWING VARICELLA IS LIFE-LONG: GETS VARICELLA ONLY ONCE AND ZOSTER USUALLY ONLY ONCE

2. FREQUENCY OF ZOSTER INCREASES WITH AGE (WANING IMMUNITY)

DIAGNOSIS

1. CLINICAL OBSERVATIONS

2. TZANCK SMEAR-LOOK FOR MULTINUCLEATED GIANT CELLS

3. ISOLATION OF VIRUS IN CELL CULTURE AND IDENTIFICATION WITH SPECIFIC ANTISERUM

1. NO ANTIVIRAL THERAPY

2. ACYCLOVIR-REDUCE DURATION AND SEVERITY

3. FOSCARNET IF RESISTANT TO ACYCLOVIR

4. FAMVIR, VALTREX-ACCELERATE HEALING OF ZOSTER LESIONS

PREVENTION

1. TWO VACCINES

a. LIVE ATTENUATED VARIVAX-PREVENT VARICELLA

b. LIVE ATTENUATED ZOSTAVAX-PREVENT ZOSTER (DOES NOT ERADICATE LATENT STATE)

1. HERPES VIRUS

2. LINEAR dsDNA, ENV, ICOSA

EXANTHEM SUBTUM OR ROSEOLA INFANTUM

LIFE CYCLE SEE HSV

HALLMARKS OF DISEASE

1. PRIMARY INFECTION OCCURS EARLY IN LIFE AS MATERNAL AB TITERS DECLINE

2. TRANSMITTED IN SALIVA; ENTERS THROUGH NASO- OR OROPHARYNGEAL MUCOSA

3. MOTHER TO OFFSPRING TRANSMISSION CAN OCCUR BY INTRAUTERINE TRANSPLACENTAL ROUTE OR INTRAPARTUM CONTACT WITH VIRUS IN GENITAL TRACT SECRETIONS OR INFECTED MUCOSA

4. REPLICATE SLOWLY AND INFECT MANY CELLS: MUCOSAL EPI CELLS (ENTRY AND SHEDDING), SALIVARY GLAND CELLS (SHEDDING), ENDOTHELIAL CELLS (RASH), AND MONONUCLEAR CELLS (6 LATENTLY INFECTS MACROPHAGES, 7 LATENTLY INFECTS CD4 CELLS)

5. VIRUS SPREADS FROM MUCOSAL EPI TO BLOOD OR LYMPH TO LYMPHOID TISSUES AND ENDOTHELIAL CELLS (MULTIPLE SITES OF LATENCY)

6. PRIMARY DISEASE: 1 WK INCUBATION THEN SUDDEN FEVER FOR SEVERAL DAYS, THEN SUDDEN RASH APPEARS ON TRUNK AS FEVER DECLINES

8. TX OF ORDINARY SUPPORTIVE CARE

9. SEROPREVALENCE INCREASES AFTER 6 MOS. OF AGE (MOST ARE SEROPOSITIVE BY 4 YEARS)

10. NO VACCINE DUE TO DISEASE MILDNESS AND FEW COMPLICATIONS

1. RHABDOVIRUS FAMILY

2. (-) SSRNA

• 3. ENVELOPED, BULLET-SHAPED VIRION, HELICAL CAPSID
• RHABDOVIRUS

BULLET; LARGE

(-)ssRNA, ENV, HELICAL

1. RABIES VIRUS ATTACHES TO ACETYLCHOLINE RECEPTOR ON CELL SURFACE

2. ENTERS AT PM BY RECEPTOR-MEDIATED ENDOCYTOSIS

3. AFTER UNCOATING FROM ENDOSOME, VIRAL RNA POL. SYNTHESIZES FIVE MRNA’S THAT CODE FOR VIRAL PROTEINS

4. REPLICATION OF VIRAL GENOME BY VIRAL RNA POL.

5. PROGENY RNA ASSEMBLED WITH VIRION PROTEINS IN CYTO

6. ENVELOPE IS ACQUIRED BY BUDDING FROM PM

ROUTE OF INFECTION

• 1. TRANSMITTED BY BITE OF RABID ANIMAL THAT MANIFESTS AGGRESSIVE BEHAVIOR INDUCED BY ENCEPHALITIS (WILD ANIMALS-RACCOONS, SKUNKS, BATS, FOXES, COYOTES)-VIRUS IN
• SALIVA

2. NOT MANY CATS AND DOGS BECAUSE THEY HAVE BEEN IMMUNIZED

3. SOME NON-BITE EXPOSURE BY AEROSOLS OF BAT SECRETIONS CONTAINING RABIES VIRUS

4. NO VIREMIC STAGE

SYMPTOMS AND HALLMARKS OF DISEASE

1. LOCAL REPLICATION OF VIRUS AT SITE OF BITE (MUSCLE, CT)

2. ATTACHMENT TO SENSORY NERVE ENDINGS BY ACH RECEPTOR AND TRANSPORT VIA AXONS TO CNS

3. REPLICATION IN SPINAL CORD AND BRAIN (HIPPOCAMPUS) AND FORMATION OF NEGRI BODIES (EOSINOPHILIC INCLUSION BODIES IN INFECTED NEURONS)

4. TRANSPORT THROUGH PERIPHERAL NERVES TO SALIVARY GLANDS (INCREASED SECRETION FOR TRANSMISSION) AND OTHER ORGANS (KIDNEY, LUNG, PANCREAS, EYE, SKIN, ETC)

5. ENCEPHALITIS DEVELOPS WHILE IN CNS, NEURON DESTRUCTION AND DEMYELINATION

• 6. VARIABLE INCUBATION PERIOD>PRODROMAL PERIOD OF FEVER, ANOREXIA, ETC.>CONFUSION,
• LETHARGY, INCREASED SALIVATION, PAINFUL MUSCLE SPASMS UPON SWALLOWING (DEVELOP HYDROPHOBIA, DON’T WANT TO SWALLOW WATER BECAUSE IT IS TOO PAINFUL)>SEIZURES, PARALYSIS, COMA

PRINCIPLE HOST DEFENSE

1. NO REAL INFO BECAUSE MOST HAVE NOT SURVIVED TO ENDURE 2ND BITE

DIAGNOSIS

1. FLUORESCENT AB STAINING OF BIOPSY SPECIMEN, USUALLY TAKEN FROM SKIN OF NECK AT HAIRLINE

2. ISOLATION OF VIRUS FROM SOURCES SUCH AS SALIVA

3. RISE IN TITER OF AB TO VIRUS

4. NEGRI BODIES DEMONSTRATED IN CORNEAL SCRAPINGS OR IN AUTOPSY SPECIMENS

INTERESTING FACTS ABOUT VIRUS

1. NEGRI BODIES

2. WHILE IN NEURONS, VIRUS IS SHIELDED FROM IMMUNE SYSTEM (LACK OF IMMUNE RESPONSE)

3. FURIOUS RABIES (80%) HYPERACTIVITY, AGGRESSIVENESS; VIRUS REPLICATES IN LIMBIC SYSTEM (INCLUDING HIPPOCAMPUS AND AMYGDALA) THAT CONTROLS EMOTION

4. DUMB RABIES (20%)-PROGRESSIVE PARALYSIS; VIRUS REPLICATES IN NEOCORTEX (PART OF CEREBRAL CORTEX THAT GOVERNS CONSCIOUS THOUGHT AND LANGUAGE, ETC.)

1. NO ANTIVIRAL THERAPY; JUST SUPPORTIVE CARE

PREVENTION

1. PRE-EXPOSURE=VACCINE GIVEN TO HIGH-RISK INDIVIDUALS (VETS)-3 DOSES

2. POST-EXPOSURE=HUMAN DIPLOID CELL VACCINE (HDCV-INACTIVATED VIRUS) (5 DOSES) + HUMAN RABIES IMMUNE GLOBULIN (1 DOSE) GIVEN AT BITE SITE

encephalitis,

• hemorrhagic fever, mild fever with muscle and
• joint pain

non-hemorrhagic rash

BUNYA

(-)ssRNA; ENV; 3 SEGS, HELICAL

a. ROBOVIRUS-RODENT-BORNE

• b. KOREAN HEMORRHAGIC FEVER (HEADACHE, PETECHIAL HEMORRHAGES,
• SHOCK, RENAL FAILURE)

c. RECENT OUTBREAK IN WESTERN US CHARACTERIZED BY FLU-LIKE SX FOLLOWED BY ACUTE RESPIRATORY FAILURE

SIN NOMBRE VIRUS (IN DEER MICE)

ACQUIRED BY INHALING AEROSOLS OF MICE URINE/FECES

DIAGNOSIS BY DETECTING VIRAL RNA IN LUNG TISSUE WITH PCR ASSAY OR BY DETECTING IGM IN SERUM

NO EFFECTIVE DRUG

NO VACCINE

FLAVIVIRUS

(+) ssRNA NON-SEG; ENV, ICOSA

a. WILD BIRDS (CROWS) ARE MAIN RESERVOIR AND VIRUS IS TRANSMITTED BY BITES OF CULEX MOSQUITOES

b. FEVER, CONFUSION, STRIKING MUSCLE WEAKNESS (ENCEPHALITIS)

c. LIFE CYCLE

BINDING TO CELL RECEPTOR AND ENDOCYTOSIS

VIRION-ENDOSOME MEMBRANE FUSION AND UNCOATING IN CYTOPLASM

• GENOME RNA ACTS AS mRNA AND IS TL BY
• RIBOSOMES IN CYTO INTO PROTEIN (CLEAVED BY PROTEASES)

MEMBRANE-ASSOC. REPLICATION

VIRION MORPHOGENESIS IN IC VESICLES; VIRION TRANSPORT AND GLYCOPROTEIN MATURATION; VESICLE FUSION WITH PM AND RELEASE

d. DIAGNOSIS BY ISOLATION OF VIRUS FROM BRAIN TISSUE,ETC. OR BY DETECTION OF AB IN CSF

e. NO ANTIVIRAL THERAPY OR VACCINE (SCREEN DONATED BLOOD FOR WNV)

WN - CROWS, FLAVI

EASTERN EQUINE ENCEPH - BIRDS; MOST SEVERE WITH 50% FATALITY, 5 CASES PER YR

WESTERN EQUINE ENCEPH- BIRDS - NO RECENT CASES

ST. LOUIS ENCEPH (FLAVI) - SPARROWS URBAN AREAS. 10-30 CASES PER; FLAVI

CALIF ENCEPH - RODENTS, 40-80 CASES PER

FLAVI

(+)ssRNA; ENV; ICOSA

a. NOT ENDEMIC TO US; IN TROPICAL AREAS

b. AEDES MOSQUITO AS VECTOR

• c. CLASSIC DENGUE-SUDDEN FLU-LIKE SX WITH FEVER, MALAISE, COUGH, HEADACHE; SEVERE JOINT AND MUSCLE PAIN (BREAKBONE), ENLARGED LN’S, PETECHIAL RASH; SX USUALLY REGRESS
• AFTER ABOUT A WEEK

d. DENGUE HEMORRHAGIC FEVER-MORE SEVERE WITH HIGHER FATALITY; INITIAL LIKE CLASSIC DENGUE THEN SHOCK AND HEMORRHAGE IN GI AND SKIN (INCREASED VASCULAR PERMEABILITY AND DROP IN BLOOD PRESSURE AND BLOOD VOLUME); MAY SEE PLEURAL EFFUSION

DENGUE SHOCK SYNDROME-CROSS-REACTING AB AT TIME OF 2ND INFECTION THAT FORMS AG-AB COMPLEXES THAT ACTIVATE A LOT OF COMPLEMENT AND BIND AND ACTIVATE MACROPHAGES (CYTOKINE STORM-MASSIVE INTERNAL BLEEDING AND SHOCK)

(+)ssRNA NON-SEG; ENV, ICOSA


1. EASTERN AND WESTERN EQUINE ENCEPHALITIS VIRUS

a. EEE CAUSES MOST SEVERE DISEASE

b. TRANSMITTED BY CULISETA MOSQUITO WITH WILD BIRD RESERVOIR

c. ENCEPHALITIS CHARACTERIZED BY SUDDEN ONSET OF FEVER, NAUSEA, VOMITING, HEADACHE

d. CHANGES IN MENTAL STATUS SOON FOLLOW; RAPID DOWNHILL COURSE WITH STIFF NECK, SEIZURES, COMA

e. IMMUNITY FOLLOWING INFECTION IS LIFE-LONG

• f.
• DIAGNOSIS MADE BY VIRAL ISOLATION OR
• DETECTING RISE IN AB TITER

g. NO ANTIVIRAL THERAPY; KILLED VACCINE ONLY FOR HORSES

COLORADO TICK FEVER VIRUS

FILOVIRUS FAMILY

(-)ssRNA LINEAR NON-SEG, ENV

LONG FILAMENTOUS STRUCTURE

HELICAL

CAUSE HEMORRHAGIC FEVER

1. BEGINS WITH FEVER, HEADACHE, VOMITING, DIARRHEA

2. BLEEDING INTO GI TRACT

3. SHOCK AND DISSEMINATED INTRAVASCULAR COAGULATION

4. TRANSMISSION BY BATS (?) OR SECONDARY TRANSMISSION BY PATIENT’S BLOOD OR SECRETIONS

5. FATAL BECAUSE OF CYTOKINE STORM OF TNF-ALPHA, IL-6, IL-8; ATTACK ON ENDOTHELIUM, AND EVENTUAL VASCULAR INSTABILITY AND COLLAPSE

LYMPHOCYTES KILLED AND AB RESPONSE RENDERED INEFFECTIVE

DIAGNOSIS BY ISOLATION OF VIRUS OR DETECTING RISE IN AB TITER

NO ANTIVIRAL THERAPY; VARIABLE RESULTS WITH IMMUNE SERUM GLOBULIN

PREVENTION BY LIMITING SECONDARY SPREAD BY PROPER HANDLING OF PATIENT’S SECRETIONS AND BLOOD; NO VACCINE

BRICK-SHAPED PARTICLES

LINEAR DSDNA, A DISK-SHAPED CORE WITHIN A DOUBLE MEMBRANE, AND A LIPOPROTEIN ENVELOPE

LARGE AND VERY COMPLEX, INDUCING BOTH SPECIFIC AND CROSS-REACTING AB’S

FAMILY CONSISTS OF THREE VIRUSES:

1. VARIOLA (SMALLPOX) VIRUS

a. LIFE CYCLE

PENETRATION OF CELL AND UNCOATING

VIRION DNA-DEP. RNA POL. SYNTHESIZES EARLY NON-STRUCTURAL MRNA THAT IS TL IN THE CYTO TO PROTEIN (ENCODE PROTEINS NECESSARY FOR REPLICATION)

VIRAL REPLICATION IN THE CYTOPLASM

• LATE GENES EXPRESSED AFTER GENOME IS
• REPLICATED AND ENCODE STRUCTURAL PROTEINS

VIRION ASSEMBLES IN THE CYTO AND MOVES TO PM BY ACTIN FILAMENTS (RELEASE AND ACQUIRE ENVELOPE BY BUDDING)

b. ROUTE OF INFECTION

TRANSMITTED BY RESPIRATORY AEROSOL OR DIRECT CONTACT WITH LESIONS OR ON FOMITES SUCH AS BEDDING

• VIRUS INFECTS URT>LOCAL LN’S>BLOOD
• (PRIMARY VIREMIA)>INTERNAL ORGANS>BLOOD (SECONDARY VIREMIA)>SKIN

c. SYMPTOMS AND HALLMARKS OF DISEASE

INCUBATION PERIOD ABOUT 7-14 DAYS

SUDDEN ONSET OF PRODROMAL SX SUCH AS FEVER AND MALAISE

SX FOLLOWED BY RASH-VIRAL REPLICATION IN SKIN AND DAMAGE BY CTL KILLING OF VIRALLY-INFECTED CELLS (RASH WORSE ON FACE AND EXTREMITIES-CENTRIFUGAL)

RASH PASSES THROUGH STAGES FROM MACULES TO PAPULES, VESICLES, PUSTULES, AND CRUSTS AFTER 2-3 WKS

d. PRINCIPLE HOST DEFENSE

AB AGAINST VIRUS PROVIDES LIFE-LONG IMMUNITY

e. DIAGNOSIS

GROWING VIRUS IN CELL CULTURE

DETECTING VIRAL AG IN VESICULAR FLUID BY IMMUNOFLUORESCENCE

TREATMENT

NO ANTIVIRAL THERAPY

g. PREVENTION

LIVE, ATTENUATED VACCINE WITH VACCINIA VIRUS GIVEN INTRADERMALLY

FORMATION OF VESICLE INDICATES SUCCESS

AN EXPOSED INDIVIDUAL CAN BE IMMUNIZED AS LONG AS 4 DAYS AFTER EXPOSURE AND BE FINE

• VACCINIA IMMUNE GLOBULINS USED FOR
• COMPLICATIONS (ENCEPHALITIS, GENERALIZED VACCINIA, ETC.)

CONTRAINDICATIONS FOR VACCINATION: ECZEMA, ATOPIC DERMATITIS, OTHER ACUTE, CHRONIC, OR EXFOLIATIVE SKIN CONDITIONS; PREGNANCY, IMMUNODEFICIENCY OR SUPPRESSION

h. INTERESTING FACTS ABOUT VIRUS

REPLICATION IN THE NUCLEUS

ERADICATED IN 1979 BECAUSE OF ADVENT OF VACCINE

GOOD VACCINE:

1. HUMANS ARE ONLY RESERVOIR

2. DISEASE IS RECOGNIZED EASILY FOR PURPOSES OF VACCINATION OR QUARANTINE

3. ACUTE INFECTIONS RESULT IN EITHER DEATH OR LIFE-LONG IMMUNITY (NO CARRIER STATE)

4. VACCINIA VIRUS IS HIGHLY IMMUNOGENIC AND MINIMALLY PATHOGENIC (EFFECTIVE VACCINE)

IMMUNE EVASION BY ENCODING PROTEINS (“VIRORECEPTORS”)-RECEPTORS FOR MAJOR CYTOKINES TGF-BETA, IFN-GAMMA, IL-1, AND COMPLEMENT –INHIBIT CYTOKINES

ORTHOPOX

BRICK/DUMBBELL; COMPLEX

ldsDNA; REP IN CYTO

a. VIRTUALLY NON-PATHOGENIC FOR HUMANS

b. USED FOR STUDIES ON POXVIRUS REPLICATION AND USED TO MAKE VACCINE

c. DEMONSTRATES SIGNIFICANT RESISTANCE TO EFFECTS OF IFN

BRICK OR DUMBBELL-SHAPED

lcdDNA; REP IN CYTO

a. TRANSMITTED BY CONTACT WITH INFECTED ANIMALS (BITE OR CONTACT WITH LESIONS OR BODY FLUIDS)

b. COWPOX-VESICULAR LESIONS ON UDDERS OF COWS; SIMILAR LESIONS ON PPL WHO MILK COWS

c. ORF VIRUS-CAUSE OF CONTAGIOUS PUSTULAR DERMATITIS IN SHEEP AND VESICULAR LESIONS IN SHEEPSHEARERS

• d. MONKEYPOX-DISEASE OF MONKEYS AND RODENTS IN CENTRAL AND WEST AFRICA; BEGINS WITH FEVER, HEADACHE,
• MUSCLE ACHES, SWOLLEN LN’S, ETC.; 1-3 DAYS AFTER FEVER, PAPULAR RASH APPEARS AND MAY BECOME VESICULAR (ILLNESS LASTS 2-4 WKS)

DISEASE CAN ALSO BE SPREAD PERSON-TO-PERSON (RESP. DROPLETS OR CONTACT WITH INFECTED BODY FLUIDS)

TESTS INCLUDE PCR-BASED ASSAY, EM, GENE SEQUENCING, IMMUNOHISTOCHEM, SEROLOGIC

NO PROVEN TX; SMALLPOX VACCINE REDUCES RISK (NO RECOMMENDATION FOR PRE-EXPOSURE VACCINE)

1. TOGAVIRUS FAMILY

2. (+)ssRNA, NON-SEG, ENV, ICOSA, E1 AND E2 SPIKES

LIFE CYCLE

1. ATTACH TO CELL SURFACE VIA SPECIFIC RECEPTORS AND ENTER HOST CELLS VIA ENDOCYTOSIS

• 2. ACIDIFICATION OF ENDOSOME RESULTS IN FUSION OF VIRAL ENVELOPS WITH ENDOSOME AND RELEASE OF
• VIRION

• 3. WHEN RELEASED FROM CAPSID, IMMEDIATE PRODUCTION VIA HOST CELL
• POL OF NON-STRUCTURAL PROTEINS, MADE AS ONE BIG PROTEIN AND CUT INTO FRAGMENTS, INCLUDING VIRAL RNA POL. (REPLICASE)

4. TC/TL OF LATE PROTEINS INTO ONE BIG PROTEIN AND CUT INTO E1, E2, AND CAPSID

5. ASSEMBLY AND BUDDING OF NEW VIRIONS

ROUTE OF INFECTION

1. TRANSMITTED BY RESPIRATORY DROPLETS AND FROM MOTHER TO FETUS

2. INITIAL REPLICATION IN NASOPHARNYX AND LOCAL LN’S>BLOOD>INTERNAL ORGANS AND SKIN (RASH)

SYMPTOMS AND HALLMARKS OF DISEASE

1. RUBELLA

a. MILDER, SHORTER DISEASE THAN MEASLES

b. INCUBATION PERIOD OF 14-21 DAYS; BRIEF PRODROMAL PERIOD OF FEVER AND MALAISE FOLLOWED BY MACULOPAPULAR RASH (PROGRESSES DOWNWARD)

c. RASH TYPICALLY LASTS 3 DAYS

d. POLYARTHRITIS CAUSED BY IMMUNE COMPLEXES IN ADULTS (ESP. WOMEN)

2. CONGENITAL RUBELLA SYNDROME

a. NON-IMMUNE PREGNANT WOMAN IS INFECTED DURING 1ST TRIMESTER (WORST TIME BECAUSE ORGANS ARE DEVELOPING)

• b. COMMON DEFECTS INCLUDE: DEAFNESS, EYE ABNORMALITIES LIKE CATARACTS, CONGENITAL HEART
• DISEASE (PATENT DUCTUS ARTERIOSUS), LOW BIRTH WEIGHT, MICROCEPHALY, ETC.

c. MECHANISM UNKNOWN; RUBELLA VIRUS ABLE TO INDUCE APOPTOSIS IN CELLS THAT MIGHT BE CONNECTED WITH P53

PRINCIPLE HOST DEFENSE

1. NATURAL INFECTION PROVIDES LIFE-LONG IMMUNITY

2. MATERNAL AB (IGG!) CROSSES PLACENTA AND PROTECTS NEWBORN

DIAGNOSIS

1. GROWN IN CELL CULTURE (MEASURE ABILITY TO INTERFERE WITH ECHOVIRUS CPE)

• 2. FOUR-FOLD OR GREATER RISE IN AB TITER BETWEEN ACUTE AND CONVALESCENT SERA IN ELISA OR
• HA INHIBITION

• 3. PRESENCE OF AB IN PREGNANT WOMAN: IGM IS RECENT INFECTION AND IGG INDICATES IMMUNITY AND
• PROTECTION OF BABY

TREATMENT

1. NO ANTIVIRAL THERAPY

PREVENTION

• 1. IMMUNIZATION WITH LIVE, ATTENUATED VACCINE-GIVEN SUBCUTANEOUSLY AT 15 MONTHS (IN COMBINATION WITH MEASLES AND MUMPS) AND TO UNIMMUNIZED YOUNG ADULT WOMEN IF THEY ARE NOT
• PREGNANT AND WILL USE CONTRACEPTION FOR NEXT 3 MONTHS

INTERESTING FACTS ABOUT VIRUS

1. CAUSES SEVERE MALFORMATIONS IN FETUS, ESPECIALLY DURING 1ST TRIMESTER

1. PARVOVIRUS

2. SMALL NON-ENV WITH (-)ssDNA; ICOSAHEDRAL CAPSID (ONLY ONE SEROTYPE)

LIFE CYCLE

1. AFTER ADSORPTION TO HOST CELL RECEPTORS, VIRION PENETRATES AND MOVES TO NUCLEUS, WHERE REPLICATION OCCURS (PENETRATION MEDIATED BY PHOSPHOLIPASE A2 ACTIVITY CARRIED ON AMINO-TERMINAL PEPTIDE OF CAPSID VP1)

2. NON-STRUCTURAL, REPLICATION, STRUCTURAL PROTEINS

3. SINGLE-STRANDED DNA HAS HAIRPIN LOOPS AT BOTH ENDS THAT PROVIDE AREAS TO INITIATE REPLICATION

4. VIRAL MRNA SYNTHESIZED BY CELLULAR RNA POLYMERASE FROM dsDNA INTERMEDIATE

5. PROGENY VIRIONS ASSEMBLED IN NUC

6. RELEASE BY CELL LYSIS

ROUTE OF INFECTION

• 1. TRANSMITTED PRIMARILY BY RESPIRATORY ROUTE, TRANSPLACENTAL, AND BLOOD TRANSFUSIONS (HUMANS
• ARE NATURAL RESERVOIR)

2. VIRUS INFECTS RBC PRECURSORS (ERYTHROBLASTS) IN BONE MARROW, CAUSING APLASTIC ANEMIA, AND ENDOTHELIAL CELLS IN BLOOD VESSELS, CAUSING RASH

SYMPTOMS AND HALLMARKS OF DISEASE

1. ERYTHEMA INFECTIOSUM (SLAPPED CHEEK SYNDROME, FIFTH DISEASE)

a. MILD DISEASE PRIMARILY IN CHILDHOOD CHARACTERIZED BY BRIGHT RED RASH, PRIMARILY ON THE CHEEKS, AND FEVER, RUNNY NOSE, AND SORE THROAT

b. “LACY” RASH ON BODY

c. SX RESOLVE IN ABOUT A WEEK

d. FIFTH DISEASE OF MACULOPAPULAR RASH IN CHILDHOOD (OTHER FOUT ARE MEASLES, RUBELLA, SCARLET FEVER, AND ROSEOLA)

2. APLASTIC ANEMIA

a. REALLY AFFECT CHILDREN WITH CHRONIC ANEMIA LIKE SICKLE CELL ANEMIA

3. FETAL INFECTIONS

a. FETAL DEATH DURING 1ST TRIMESTER

b. HYDROPS FETALIS DURING 2ND SEMESTER

MASSIVE EDEMA OF FETUS SECONDARY TO CHF FROM SEVERE ANEMIA BY B19-KILLED ERYTHROBLASTS

c. NO IMPORTANT CLINICAL FINDINGS DURING 3RD TRIMESTER

4. ARTHRITIS

a. IMMUNE COMPLEXES OF VIRUS AND IGM OR IGG CLOGGED IN SMALL JOINTS OF FEET AND HANDS BILATERALLY

b. MOSTLY IN WOMEN

5. CHRONIC B19 INFECTION

a. PEOPLE WITH IMMUNODEFICIENCY (AIDS, TRANSPLANT, ETC)

PRINCIPLE HOST DEFENSE

1. AB (IGM, IGG) PROVIDE LIFE-LONG IMMUNITY

DIAGNOSIS

1. FIFTH DISEASE AND APLASTIC ANEMIA BY DETECTING IGM AB

2. B19 ISOLATION FROM THROAT SWABS (NOT USUALLY DONE)

3. VIRAL DNA IN BLOOD OR AMNIOTIC FLUID BY PCR

TREATMENT

1. NO SPECIFIC TX

ORTHOPOX

BRICK/DUMBBELL; COMPLEX

ldsDNA

2. MOLLUSCUM CONTAGIOSUM VIRUS-BENIGN EPIDERMAL TUMOR

• a.
• FLESH-COLORED PAPULE ON SKIN OR MUCOUS MEMBRANE THAT IS PAINLESS,
• NON-PRURITIC, AND NOT INFLAMED (UMBILICATED/ CUP-SHAPED CRATER WITH
• WHITE CORE)-SELF-LIMITING BUT CANLAST FOR MONTHS

b. LESION COMPOSED OF HYPERPLASTIC EPITHELIAL CELLS WITH EOSINOPHILIC INCLUSION BODY INSIDE (CONTAINS PROGENY MCV)

c. TRANSMITTED BY CLOSE PERSONAL CONTACT, INCLUDING SEXUALLY, AND INDIRECT CONTACT (SHARING TOWELS, CLOTHING)

d. DISEASE COMMON IN CHILDREN, CAUSING LESIONS AROUND EYES AND ON TRUNK (ADULT LESIONS IN GENITAL AREA-MORE INFLAMED)

e. LESIONS CAN BE WIDESPREAD IN PPL WITH LOW CMI RISING CASES AS STD AND IN AIDS PTS

g. VIRUS IS POOR IMMUNOGEN; ABOUT 1/3 OF PTS. NEVER PRODUCE AB’S AGAINST IT AND CAN GET SUBSEQUENT INFECTIONS

• h. DIAGNOSIS MADE CLINICALLYREMOVAL
• OF LESIONS BY CURETTAGE OR LIQUID NITROGEN

NO ANTIVIRAL THERAPY; CIDOFOVIR AND HAART MAY HELP IN IMMUNOCOMPROMISED PTS; NO VACCINE

ZOONOTIC

2X (-)ssRNA; ENV, HELICAL CAPSID

LASSA FEVER VIRUS-HEMORRHAGIC FEVER

LYMPHOCYTIC CHORIOMENINGITIS VIRUS-ASEPTIC MENINGITIS

c. MINOR VIRAL PATHOGENS