The first viral diseases to be investigated were:
- Rabies by Pasteur
- Yellow Fever by Walter Reed
Viruses are non-living intracellular parasites that cannot be cultivated in cell-free media. Where must they be grown?
Must be grown in tissue culture, frequently grown in embryonated bird eggs
Viruses are Small in size, largest is about
A single virus particle is referred to as a
Genome is either?
RNA OR DNA, but not both
Nucleic acid is enclosed in?
protein coat called a capsid (nucleic acid + capsid = nucleocapsid)
Some viruses have lipoprotein envelope, from where?
acquired from host cell
Envelope has what features?
glycoprotein spikes for interaction with host cell
Viruses with a capsid, but no envelope are called
Two primary types of symmetry of capsid
- 1. helical
- 2. icosahedral
Viruses have different shapes, name the three
spherical, bullet shaped, or filamentous
- Agents with no detectable nucleic acid
- Appears to be self-replicating protein
- Some scientists believe a relationship to viruses exists
- Responsible for the neurodegenerative diseases classified as spongiform encephalopathies (SE). Diseases cause holes in tissue, brain appears as a sponge
- SEs include mad-cow disease, Creutzfeldt-Jacob, Kuru, scrapie
Much of our understanding of How Viruses Replicate and Multiply comes from?
studying bacteriophages (bacterial viruses)
The Lytic Cycle of Bacteriophages: Adsorption – is defined as what?
bacteriophage irreversibly adsorbs to receptor site using tail fibers
The Lytic Cycle of Bacteriophages: Adsorption –Various receptor sites include?
- Lipopolysaccharide of Gram neg. cells
- Pili and flagella
Beginning of latent period- latent period continues until cell lyses: When does this begin?
The Lytic Cycle of Bacteriophages: Adsorption
The Lytic Cycle of Bacteriophages: Penetration – is defined as what?
phage tail penetrates bacterial cell, nucleic acid enters leaving capsid on outside of host cell
The Lytic Cycle of Bacteriophages: Penetration, Beginning of eclipse period – Define it?
defined as period during which no viral particles can be found either inside or outside cell, viral DNA is taking over machinery of host cell
What occurs during the The Lytic Cycle of Bacteriophages: Penetration: Eclipse Period?(2)
- First mRNA is transcribed to code for a repressor enzyme to prevent entry of other phages
- Second additional enzymes are produced to depolymerize host cell DNA.
Destruction of host cell DNA leads to?(4)
- Halt of host cell metabolism
- Virus assuming control of host cell metabolism
- Viral nucleic acid being assembled using host nucleotides
- Use of host cell ribosomes for translation of viral mRNA
The Lytic Cycle of Bacteriophages: Prefabrication, What occurs?(3)
- Viral genome is replicated multiple times
- Necessary viral mRNA is synthesized
- All viral parts are “prefabricated”
The Lytic Cycle of Bacteriophages: Maturation, What occurs?(3)
- End of the eclipse period
- New viruses are assembled
- Viruses DO NOT grow, cells grow, viruses are assembled
The Lytic Cycle of Bacteriophages: Viral release, What occurs?(4)
- End of latent period
- New viruses produce lysozyme
- Lysozyme causes the bacterial cell wall to rupture
- Viruses are released
ANIMAL VIRUSES - Adsorption, What Occurs?
- Host cell receptors are normal surface molecules involved in routine cellular function
- Naked virus – capsid proteins bind to host cell receptors
- Enveloped virus – glycoprotein spikes bind to host cell receptors
ANIMAL VIRUSES - Penetration and uncoating, what occurs with Naked Viruses?
Naked viruses undergo a major change in capsid structure on adsorption to plasma membrane, so that their nucleic acids are released into the cytoplasm
ANIMAL VIRUSES - Penetration and uncoating, what occurs with Enveloped Viruses?
- Enveloped viruses enter the host cell in one of two ways
- viral envelope may fuse with the host cell cytoplasmic membrane and the nucleocapsid is released into the cytoplasm
- animal viruses enter by endocytosis whereby the host cell cytoplasmic membrane invaginates and pinches off, placing the virus in an endocytic vesicle. Lysosomes fuse with vesicle and uncoat releasing nucleic acid
ANIMAL VIRUSES - Synthesis (Replication) DNA Viruses, give the rundown.
- Early synthesis = host cell is overtaken- viral DNA is synthesized and transcribed to RNA, inhibit host cell DNA, RNA and protein synthesis
- Viral DNA replication usually occurs in host nucleus (exception = poxviruses are replicated in the cytoplasm)
- DNA viruses often remain latent in the infected cell
- Early viral genes transcribe DNA binding proteins and enzymes
- Late viral genes transcribe structural proteins
ANIMAL VIRUSES - Synthesis (Replication) RNA Viruses: Name the Four Groups of RNA
- Positive (sense) strand RNA viruses
- Double stranded RNA viruses
- Negative (antisense) strand RNA viruses
ANIMAL VIRUSES - Synthesis (Replication) RNA Viruses: Positive strand virus replication, rundown?
- (+) strand is used as giant mRNA
- Host ribosome translates giant mRNA into various viral enzymes
- RNA polymerase produces a (-) strand RNA
- The (-) strand is then used to synthesize more (+) strands to be used as mRNA or to be inserted into new viruses
ANIMAL VIRUSES - Synthesis (Replication) RNA Viruses: ds RNA, rundown?
- These viruses (reoviruses) have a transcriptase that copies the (-) strand of their genome to generate mRNA
- mRNA is translated into various enzymes to synthesize new viruses
ANIMAL VIRUSES - Synthesis (Replication) RNA Viruses: Negative strand virus replication, Rundown?
- A viral transcriptase converts (-) strand RNA to (+) strand RNA
- The (+) strand acts as mRNA
- A viral replicase produces double stranded RNA (+/-) that assembles new viruses
ANIMAL VIRUSES - Synthesis (Replication) RNA Viruses: Retroviruses, Rundown?
- Possess single stranded (+) RNA genome
- Synthesize mRNA and replicate RNA genome by converting RNA to DNA
- Reverse transcriptase converts (+) RNA to (-) DNA
- The (-) DNA is copied to create a double stranded DNA called proviral DNA
- Proviral DNA synthesizes (+) RNA genome for new viruses
ANIMAL VIRUSES - Maturation - Assembly of new viruses - Capsid formation, How is it done?
- Capsid protein synthesis is directed by late genes (structural)
- Spontaneously self-assemble- capsid around nucleic acid
- Location of maturation is virus specific
ANIMAL VIRUSES - Maturation - Assembly of new viruses - If Enveloped: How is it done?
- Late viral mRNA transcribes glycoproteins
- Glycoproteins are inserted into the host cell membrane
- Virus particle acquires the glycoprotein envelope during exocytosis
ANIMAL VIRUSES - Viral release - Naked virus, how is it done?
infected cell usually lyses and the virions are released
ANIMAL VIRUSES - Viral release - Enveloped virus, how is it done?
- The host cell may or may not be lysed
- Virus obtains its envelope by budding from membrane bound organelles within the cell
- Transport vesicles carry the virus to the cell surface where it is released by exocytosis
persistent infections are those in which the virus is not cleared from the host following primary infection, but remains associated with specific cells
some DNA viruses and retroviruses establish persistent infections that stimulate uncontrolled cell growth causing transformation or immortalization of the cell (cancer cells)
Define Immunological escape
many viruses have evolved systems of immunological escape to evade detection ie herpes viruses escape detection by integration into host cell DNA
Describe DNA Poxviruses
- Large brick shaped viruses – largest of all viruses, 200 nm
- Virions contain one molecule of linear double stranded DNA
Name the five DNA Pox Viruses
- Molluscum contagiosum
Describe Molluscum contagiosum
- Small pearly or flesh-colored bumps
- Contagious but is not harmful
- In people with impaired immune systems bumps can be extensive and disfiguring
- Disease caused by variola virus
- Variola major- the more severe form
- Variola minor- more mild form
- Highly contagious, respiratory secretions and direct contact transmission
- Fever, chills, nausea, severe muscle aches
- Rash begins as flat lesions, progress to papules- eruptive stage
- Papules become pustules, scab, leave scar
- In 1967, the WHO undertook a global program of smallpox vaccination. At that time, 10 to 15 million cases of the disease occurred each year, with more than 2 million deaths
- The last case of endemic smallpox was reported in Somalia in 1977
- Considered eradicated in 1980
Describe Cow pox
- Causes human disease through zoonosis
- Transmission to humans traditionally occurred via contact with the infected teats of milking cows
- Vaccinia virus is a big mystery in virology. It is not known whether vaccinia virus is the product of genetic recombination, or if it is a species derived from cowpox virus or variola virus by prolonged serial passage, or if it is the living representative of a now extinct virus.
- Vaccinia virus was used for smallpox vaccination
Describe Monkey pox
- Rare viral disease found mostly in the rain forest in west Africa.
- Called “monkeypox” because it was first discovered in laboratory monkeys in 1958
Orf is a viral pox infection of the skin contracted from sheep and goats
Describe Herpes Viruses
- A leading cause of human viral disease, second only to influenza and cold viruses
- Once a patient has become infected by herpes virus, the infection remains for life
- Icosahedral symmetry
- Single molecule of double stranded DNA
- Attracted to neurons
Name the 7 Herpes Viruses
- Cytomegalovirus (CMV)
- Varicella- Zoster Virus (VZV)
- Herpes simplex viruses (HSV)
- Epstein Barr (EBV)
- Human herpes virus 6
- Human herpes virus 7
- Human herpes virus 8
Decribe Cytomegalovirus (CMV)
- By college age, about 15% of the US population is infected and this rises to about half by 35 years of age.
- The virus is spread in most bodily secretions
- Cytomegalovirus infection is therefore sexually transmitted
- Transplacental infection - CMV can also spread to a fetus in a pregnant woman
- Most common viral cause of congenital disease (mental retardation)
- Up to one in forty newborns in the U.S. are infected by the virus
- CMV causes no symptoms in children and at most mild disease in adults
- CMV can be a major problem for those who are immunosuppressed
CMV in AIDS Patients Causes what?
Particularly important is CMV-retinitis in the eye which occurs in up to 15% of all AIDS patients
Varicella- Zoster Virus (VZV) is also known as what?
Also known as human herpes virus-3
Varicella- Zoster Virus (VZV) causes what two diseases?
VZV causes two diseases, chicken-pox, usually in childhood, and shingles, later in life
Describe Varicella- Zoster Virus (VZV) - Chicken pox
- Transmission is via respiratory droplet
- Also spread through direct contact with vesicles
- Extremely communicable, rates of infection exceeding 90% in susceptible households
- VZV spreads from the lungs by entering blood stream (viremia)
- VZV leaves the blood vessels and first infects sub-epithelial sites and then epithelial sites forming papulae, papulae becomes fluid filled vesicle
- Vesicles found on scalp (unique)
- Fluid filled vesicles become pustules, then scab
- The lesions itch, can cause bacterial superinfection
- Recover in two weeks
- Major problems may be caused by infection in utero during the first trimester
Describe Varicella- Zoster Virus (VZV) - Shingles
- Shingles is a recurrence of a latent varicella infection
- Viruses move down nerves to epidermis
- Reactivation of virus due to stress, injury, disease
- Severe radicular pain in discrete areas, those innervated by the nerve in which latent infection has occurred
Shingles follow what kind of lesion pattern?
Chicken pox-like lesions occur in restricted areas (dermatome) that are innervated by a single ganglion
How would one Diagnose- chickenpox and shingles?
Definitive diagnosis can be made by culture of the virus from the lesions, search for “giant cells” with inclusions
How would one Treat- chickenpox and shingles?
- Live attenuated vaccine available which leads to antibody production and cell-mediated immunity
- Chemotherapy includes: various nucleotide analogs
How do Herpes simplex viruses (HSV) infect?
- HSV-1 and HSV-2 first infect cells of the mucoepithelia or enter through wounds. Then frequently set up latent infections in neuronal cells
- It is often noted that HSV-1 causes infections above the waist and HSV-2 below the waist but this reflects the mode of transmission not ability of virus to cause disease
What Diseases are caused primarily by HSV-1?
- Herpes labialis = fever blisters and cold sores on lips
- Eczema herpeticum = widespread cutaneous HSV in patients with pre-existing eczema
- Keratoconjunctivitis (herpetic keratitis) = infection of the cornea
- -Leading cause of corneal blindness in industrialized nations
What Diseases are caused primarily by HSV-2
- Genital herpes
- Prodrome (early symptom, indicates onset of disease) 1-2 days of burning sensation in the area that is about to erupt
- Primary infection is characterized by viremia, fever, swollen lymph nodes, pain on urination
- Secondary episodes of genital herpes, which occur as a result of reactivation of virus, are frequently less severe (and last a shorter time) than the first episode
- Triggered by fever, menstruation, stress, UV light
- Whether there is an apparent active disease or not, an infected patient remains infectious without overt symptoms
- Herpetic Whitlow = herpes infection of fingers and hands
- Herpes gladiatorum = skin lesions contracted by wrestlers spread by direct contact
How would one Treat Herpes Infection?
- Patient counseling
- Drug treatment
- Acyclovir (valacyclovir, famciclovir …)
Lets talk about Acyclovir (valacyclovir, famciclovir …), what's it for? Details?
- Treats Herpes
- Acts as nucleotide analog, inhibits DNA polymerase
- No action against latent infection
- Does reduce symptoms
- Both oral and topical
What are the Diseases caused by Epstein Barr (EBV)?
- Infectious mononucleosis
- African-Burkitts lymphoma
- Nasopharyngeal cancer
- Hairy oral leukoplakia
Describe Infectious mononucleosis
- Infection with EBV occurs worldwide among humans and usually occurs as a subclinical infection in early childhood
- EBV is acquired by contact with infected cervical and oral secretions
- EBV infects and multiplies in the B cells in the oropharyngeal epithelium
- Most infections in young children are asymptomatic. Symptoms are more pronounced in previously uninfected young adults
- T cells increase in number in the circulation and may account for up to 80% of the white blood cells
- T cell response results in enlarged lymph glands, liver and spleen
- Activation of the T cells limits the proliferation of B cells and the disease resolves in 8-10 days
Describe African-Burkitts lymphoma
- Tumor of the jaw and face found in children
- Tumor cells show evidence of EBV DNA and tumor antigens and patients show a much higher level of anti-EBV antibodies than other members of the population
Describe Nasopharyngeal cancer
- Tumor of the epithelium of the upper respiratory tract
- Tumor cells contain EBV DNA
- May be a genetic predisposition to the development of EBV cancers or there may be an environmental cofactor involved
Describe Hairy oral leukoplakia
EBV-associated disease results in lesions in the mouth and has increased in frequency recently as it is an opportunistic infection of HIV-infected patients
What would one use to Diagnose EBV
- Elevated white count
- Atypical white blood cells- Downey cells
Describe Human herpes virus 6
Causes roseola infantum (sudden rash, 3 day fever, rose rash, 6th disease)
Describe Human herpes virus 7
HHV 7 causes no known disease
Describe Human herpes virus 8
- Formerly known as Kaposi's sarcoma associated herpes virus and is found in the saliva of many AIDS patients
- KS lesions are nodules or blotches that may be red, purple, brown, or black, usually painless but sometimes painful and swollen
- Non-enveloped viruses
- Genome is made of double-stranded DNA
- Capsid is icosahedral with 12 penton fibers that bind to receptor sites on host cell
Where do Adenoviruses attack?
- Adenovirus primarily attacks mucoepithelial cells of the conjunctiva, respiratory tract, gastrointestinal and genitourinary tracts
- Acute respiratory infection – common cold
- Pharyngitis – resembles strep throat
- Epidemic keratoconjunctivitis
What are the two Papovaviridae?
- Human Papillomavirus
Describe Human Papillomavirus(8)
- Wart-causing viruses
- Naked dsDNA virus
- Icosahedron capsid symmetry
- Replicate in squamous epithelium of skin and mucous membranes
- Different serotypes result in different type of warts
- Many people infected with HPV have no symptoms
- Papilloma viruses cause human neoplasms and cause natural cancers in animals
- Found associated with human penile, uterine and cervical carcinomas and are very likely to be their cause
Describe Common warts, two types
- Plantar warts- painful deep warts found often on the bottom of the foot
- Laryngeal papillomas- benign epithelial growths similar to warts on the skin
Describe Genital warts
- One of the most common sexually transmitted infections (STI) in the world
- About 30 types of HPV are spread through sexual contact
- Single or multiple lesions that appear in the genital areas
- Naked dsDNA viruses with icosahedral symmetry
- Natural history of human polyomaviruses remain unknown, such as the method of their transmission
- Primary polyomavirus infections have not been associated with any specific clinical syndromes
- Smallest naked icosahedral DNA viruses
- Parvoviruses are thus among the most resistant viruses known
- Infects cats, dogs, mice and humans
Describe Human parvovirus
- Parvovirus B19 has been found in the respiratory secretions (e.g., saliva, sputum, or nasal mucus) of infected persons before the onset of rash, when they appear to "just have a cold."
- Responsible for Fifth Disease
Describe Fifth Disease
- First stage – eight days after infection with parvovirus, fever cold symptoms
- Second stage – rash begins on face- called “slapped cheek”= erythema infectiosum
- Typically resolves in 1-2 weeks
Describe Paramyxoviruses, what are the three types?
- Enveloped, negative strand RNA viruses
- Helical symmetry
- Rubeola (measles) and mumps, parainfluenza
Describe Rubeola virus (measles)
- virus has hemagglutinin (surface glycoprotein) for attachment to host cell, lacks neuraminidase activity (aids in the efficiency of virus release from cells)
- The main route of infection is via inhalation of respiratory secretions
- Almost all infected individuals show signs of disease
- Highly contagious and the period of maximum contagiousness is the 2 to 3 day period before onset of the rash
Describe Measles- uncomplicated type
- Respiratory tract symptoms: running nose (coryza) and cough
- Koplik's spots on mucosal membranes small (1 - 3mm), irregular, white spots, with bluish halo
- Maculopapular rash which extends from face to the extremities
Describe Measles complication type
- Impaired cell-mediated immune response, there is continued growth of the virus in the lungs leading to giant cell pneumonia. Rare, but often fatal
- Otitis media and bacterial pneumonia are quite common
- 1 in 1000 cases may get encephalitis
Define Sub-acute sclerosing pan encephalitis, what is it associated with?
- progressive neurological disorder characterized by inflammation of the brain
- Develops 1 to 10 years after the initial infection. It is a progressive, usually fatal disease and those who survive are severely impaired mentally and physically
- Very rare
- Associated with Measles
How do you Control of Measles?
- Only one serotype (antigenic type)
- Provides life-long immunity
- Attenuated live vaccine
Four types, all of which can cause upper respiratory infections or lower respiratory infections especially important in children because it is responsible for approximately 40-50% of croup cases
- Causes swelling of salivary glands (parotid glands)
- Transmission is via respiratory secretions and saliva. It is highly contagious
- Virus infects upper/lower respiratory tract leading to local replication. The virus spreads to lymphoid tissue which leads to viremia.
What are some Complications of mumps?
- Orchitis (testicular inflammation).
- Aseptic meningitis
How do you Control mumps?
- MMR vaccine
- Single serotype of mumps
- Life long immunity
Describe Togaviridae- rubella, what else is it known as?
- (German measles)
- Positive strand RNA virus
- Icosahedral symmetry
- Only member of the Rubrivirus genus of the Togavirus family
Describe German measles
- Transmitted by respiratory secretions
- Initial site of infection is the upper respiratory tract. The virus replicates locally in the lymph nodes leading to viremia and spread to other tissues
- Rash (if it occurs) starts after an incubation period of approximately 2 weeks
Describe Congenital Infection of German Measles
- Risk to a fetus is highest in the first few weeks of pregnancy and then declines in terms of both frequency and severity, although there is still some risk in second trimester
- Virus infects the placenta and then spreads to the fetus
If non-immune mothers are infected in the first trimester, up to 80% of neonates may have defects, what are the defects?
- Hearing loss
- Mental retardation
- Congenital heart defects
- Neurologic problems
- Ophthalmic problems
- Congenital infections can infect others after birth for a year