Which strain of HIV is found worldwide and which is found in West Africa?
- HIV-1 worldwide (the one that we care more about)
- HIV-2 West Africa
Family and genus of HIV? Genome?
- Lentivirus genus
- Single stranded RNA+ (positive polarity)
T/F: HIV causes rapid infection and short incubation time
False; HIV causes slow infections (Start with very mild symptoms) and has a long latent period, aka long incubation time before (if) it progresses to AIDS
What are the receptor(s) that HIV bind to enter human cells?
- CD4 T cell receptor
- CCR5 receptor= to infect monocytes, macrophages and dendritic cells
- CXCR 4 receptor = probably the same thing as above
T/F: CD8 T cell is infected by HIV
False; CD 4 T is
Which enzyme does HIV utilize to convert its genome once inside human cell?
Reverse transcriptase which makes double stranded DNA from RNA
What is p24?
- It is a nucleocapsid protein (gag protein), that protects viral RNA
- It is also a marker for early infection detection (we have anti- p24 antibodies to look for them early on)
What is the enzyme used to incorporate viral DNA into our genome?
How does HIV enter human cells?
Gp120 and gp41, both envelope glycoproteins, work together to get the virus to bind the host cell specific receptors (Gp120), and gp41 helps with fusion of HIV into human host cell.
T/F: retrovirus envelope comes from host nuclear membrane
False; these viral envelopes come from our cell membrane; envelope from host nuclear membrane is a unique property of herpeviridae family, i.e. EBV
What are the three typical retrovirus genes?
What are proteins encoded by gag gene:
P24 nucleocapsid and p17 matrix protein
What are proteins encoded by pol gene?
Protease, integrase, reverse transcriptase polymerase
What are proteins encoded by env gene?
Glycoprotein 120 and 41
Which is the protein that gives stability to the virus?
Which is the protein that is used as an early marker for HIV detection?
Which protein cleaves viral polyproteins into their functional units after translation
Which genes are required for HIV replication?
What is the tat gene?
A required HIV replication gene for TRANSACTIVATING factor- aka production of virus
What is the rev gene?
A required HIV replication gene that regulates expression of Virion protein
What is nef?
- A notable accessory gene that is important in reducing host CD 8 cytotoxic T cell ability to attack the virus
- Can also cause CD 8 death
Which protein can induce CTL death and decrease CD4 proteins and class I MHC proteins on surface of the infected cells?
Nef, a protein product of the accessory gene nef
Which glycoprotein mutates rapidly causing antigenic variation so making it hard for our immune system to target and eradicate?
T/F: both gp 120 and P24 are proteins that mutate rapidly inducing antigenic shifts, thereby evading our immune attacks
False; only true for gp120, p24 does not vary, and we use it as a diagnostic marker in early infection
T/F: antibodies made against p24 nucleocapsid is important for our immune system to attack the virus
False; these antibodies are not protective, they just serve as a serological marker
Where does viral DNA replication occur in host cell?
T/F: people with mutations on the gene encoding CCR5 can be protected from HIV
How is HIV transmitted?
- Sexual transmission is #1. Physical breach of epithelial barrier
- They bind to dendritic cells/ macrophages and gets brought to the lymphoid tissue where they feast on all the CD4 T cells tehre
What is a pro-virus?
Virus where their RNA genome has been incorporated into our genome
What role does our acting and tubulin play in RNA infection?
These act like shuttle, basically helping viral genome to get incorporated into our nucleus
What is the function of host cell RNA polymerase in viral infection?
- Viral mRNA transcribed from the proviral DNA via host RNA polymerase
- This process is augmented by virus Tat protein
Gag and pol polyproteins are cleaved by _____, while env polyprotein is cleaved by ____.
- Viral protease
- Cellular protease
T/F: like EBV, HIV can be transmitted via saliva and kissing
False; HIV is only transmitted primarily through sexual contact, transfer of infected blood or perinatally
T/F: the most common transmission of HIV worldwide is homosexual contact
False; it is actually heterosexual worldwide, however, in the US, it is through homosexual contact
T/F: HIV infection immediately presents with flu like symptoms upon transmission
False; acute infection does not present until 2-4 weeks post-infections
What are symptoms of acute HIV infection?
- Flu like symptoms, fevers, headache, fatigue, lymphadenopathy in neck and groin
- Some with maculopapular rash on trunk, arms and legs (no palms or soles)
T/F: Acute HIV infections do not present with any hallmark symptoms, however in Chronic HIV infection, patient presents with hepatosplenomegaly and drenching night sweats
False; there is little or no symptoms again in chronic HIV infections – latent period
What is the CD 4 cell count that defines AIDS?
CD 4 cells less than 200 is AIDS-defining
AIDS patients are susceptible to which diseases?
- CMV retinitis
T/F: HIV can infect brain monocytes and macrophages which can lead to multinucleated giant cell encephalitis
T/F: much like antibiotics use, only give one HIV drug at a time to treat so to prevent resistance
False; because of HIV’s fast mutations, always give a cocktail treatment – the HAART (highly active antiretroviral therapy) or ART (antiretroviral therapy)
How can HIV evade our immune system?
- Antigenic variation
- Hide in microglial cells and T cells
- Removing MHC to avoid CD8 killing
- Decrease NK cell ligands so NK can’t kill them either
- Destroy CD 8, CD4, monocytes and macrophages
What is confirmatory diagnosis of HIV?
- HIV-1 nucleic acid test (RT-PCR)
- Western Blot for HIV proteins
At initial infection, what is the CD 4 level vs viral load
- Initially, CD 4 is low and viral load is high
- This is at around 4-8 week mark
During latent period (could last 7-10 years or lifetime if on treatment), what is CD 4 vs viral load?
- CD 4 remains high/ acceptable level
- Viral load lower
What is the acute HIV infection window period?
Lag time between exposure to HIV and presence of detectable antibodies or viral RNA
T/F: a newly infected HIV patient may have negative antibody test for p24 antigen and HIV antibody but could be positive for Viral RNA detection
True; this HIV RNA can be detected the earliest at 10 days post infection
What is the viral set point?
- It predicts the progression of AIDS progression based on cytotoxic T cell response to virus months post infection and measuring HIV RNA level
- The lower the set point, meaning CTL responds well to virus and been killing them, the slower the progression to AIDS and better prognosis
What are some factors that can cause HIV to never progress into AIDS?
- Mutated HIV-1 strains
- Having genetic mutation that does not allow the virus to even bind to cells
- Robust CD4 and CD 8 responses
T/F: in chronic/latent HIV infection, p24 antibody level remains at relatively high in order to protect the virus capsid
False; p24 goes away after the initial acute infection, will not be present at all in latent stage
Levels of virus and viral load (RNA) are ____ in early infection, _____ for several years, and _____ during AIDS
As HIV slowly progresses into AIDS (in latent stage), CD4 counts starts to _____ and risk for opportunistic infections or malignancies ______
What is TH17?
A subset of CD4+ T cell in the mucosa, HIV infection also targets these cells resulting in bacterial infection in mucous-lined area such as the colon
When does our body start to make antibodies for HIV? When does a patient become seroconverted and show positive HIV antibodies
- 2 weeks after infection (10-14 days)
- 3 to 4 weeks to have seroconverted
What to do if antibody test is negative but still suspect HIV in a patient who may have recently contracted the virus?
PCR based assay for viral RNA in the plasma
T/F: higher the set point at the end of the initial infection, the less likely the individual is to progress to symptomatic AIDS because this means the CD 8 T cells respond well
False; if high set point, this means CD 8 T is not doing shit, and patient will have a fast progression and not good prognosis. You want low set point if you want the patient to live
T/F: large amount of HIV is being produced by lymph node cells but remain within the lymph node during latent period, so the viral load remains low during this time
What is AIDS-related complex? When does it occur?
- ARC can occur during the latent period with symptoms of persistent fevers, fatigue, weight loss and lymphadenopathy
- Often progress to AIDS
Common AIDS opportunistic infections:
- Pneumocystic jiroveci (a fugnal infection)
- Mycobacterium avium
PCP can be prominent when CD4 is ______. Toxoplasma when CD 4 is ____. Mycobacterium avium and Cytomegalovirus when CD 4 is ______
- Less than 200 (PCP)
- < 100 (toxoplasma)- which is cat poop fungus
- < 50 (Mycobacterium avium and CMV)
Prophylaxis for common AIDS opportunistic infections: PCP, toxoplasma, mycobacterium avium and CMV?
- PCP- TMP-SMX
- Toxoplasma- TMP-SMX
- M. avium- Azithromycin (macrolide) + ethanmbutol
- CMV- ganciclovir
What is Kaposi’s sarcoma?
- Cancer from the lymph vessels
- Caused by human herpesvirus 8 oncogene transmitted through saliva
Clinical presentation of Kaposi sarcoma:
Red, raised bumpy rash on legs, feet or face. Can also be in genital area, mouth or LN
T/F: Over 35% of people with AIDS may get Kaposi sarcoma
True. One of the AIDS defining illnesses
T/F: Kaposi sarcoma is caused by a virus of the retroviridae family that is why it is so commonly seen in AIDS patients
False; Kaposi is caused by Human Herpesvirus 8. This just happens simply because of AIDS patient being immunocompromised and susceptible to opportunistic infections
How can PCP be diagnosed?
A fungal infection via aerosol transmission seen often in AIDS patients (CD4 < 200). Dx’d: Sputum/lavage sample – PCR
In very late stage of AIDS (CD4 < 50!), what infection may occur that otherwise never occurs with immunocompetent patients?
Mycobacterium avium and M. intracellulare; through inhalation/ ingestion, most commonly affect lungs
T/F: CD 4 is present on macrophage, monocytes, helper T cells and dendritic cells
What is the strongest indication of disease progression in AIDS?
CD 4 T cells count
What test is used to screen for HIV?
ELISA to look for antibodies against viral proteins
What are 3 mechanisms by which HIV-infected CD 4 T cells are lost?
- HIV cytopathic effect
- HIV-specific CD 8 T cell killing