HIV/AIDS Flashcards
What is the structure of the HIV virion?
enveloped, two identical strands of +ssRNA.
does the virion carry enzymes?
Yes, carries 3 enzymes: reverse transcriptase, integrase, protease.
List the life cycle steps of the HIV life cycle
attachent, co-receptor binding, fustion, reverse transcription, integration, transcription, translation, clevage of precursor proteins, nucleocapsid assembly, budding, virion maturation.
HIV: tropism?
HIV likes to infect host’s CD4+ cells.
Is binding to CD4 antigen alone enough to permit entry of HIV into host cells?
NO, must interact with host cell co-receptor, usually CCR5. Then fusion of the viral envelope occurs, resulting in nucleocapsid entry.
Once the HIV nucleocapsid is inside the host cell, what happens?
The HIV/s reverse transcriptase uses a host tRNA as a primer, and makes a sDNA copy of the RNA genome. Eventually yields a linear dsDNA copy of the HIV genome.
what helps HIV integrate into the host cell genome?
HIV integrase enzyme
For replication to occur, what needs to happen to the integrated HIV genome?
must be translated by host cell RNA polymerase to make HIV mRNA that can be translated into proteins.
what activates the expr of HIV mRNA from the integrated HIV genome?
activated CD4 cells
what does the HIV protease do?
cleaves HIV precursor proteins into mature HIV products.
How are new HIV virions formed?
by budding out of the capsid via a modified host cell plasma membrane. virion at this point is NOT fully mature
Does the reverse transcriptase that makes the DNA copy of HIV have proofreading functions? what is the result of this
NO: these replication enzymes are error prone. effect is that HIV mutates frequently. A billion HIV mutants are made daily.
DNA: transmission route?
sexual contact, infected blood
a higher risk of transmission can be attributed to what?
higher concentration of HIV aka viral load
Routes of transmission: (3+)
IV drug use
sex (vag, anal: receptive partner is at higher risk)
other includes transplacental, perinatal, breastfeeding, blood transfusions, needle stick
Prevention strategies for HIV: (3)
condoms
circumcision (in some popns)
microbicidal creams
Early HIV infection: what does it appear as?
Acute infection. can look like mono, fever, lymph nodes, fatigue
what is the level of viremia during this early phase?
extremely high.
what happens to the number of CD4+ t cells during acute HIV infection?
dramatic decrease
what does an infected person do in response to acute HIV infection?
mounts a robust immune response. following this response, viral load decreases, and the number of CD4+ t cells is partially restored back to normal
at what point does the HIV load attain its set point?
after the acute infection and subsequent immune response
does the immune system ever clear the HIV infection?
NO
what other virus does the body not ever clear?
Some of the Hep viruses: Hep A and E are cleared, Hep B can be but may not be, Hep C is not usually cleared, Hep D can be, herpes NOT cleared.
What is a predictor of progression of HIV to AIDS?
viral load
what is a proxy for the level of immunosuppression of the body in HIV/AIDS?
CD4+ counts
Measles does what to T cells?
puts them in an anergic state
IF you get a PPD test after you have just been infected with measles, will it be positive or neg? why?
negative (even if you have Tb), because the T cells are anergic and will not respond
Measles: trophism?
pantrophic
what 3 viruses are most concerning if they are transmitted transplacentally?
Rubella, CMV (1st tri is worst), parvo (problem at any point).
The decrease in viral load correlates with what
seroconversion
during chronic infection, HIV replication is extensive in what tissue
lymphoid
how do we diagnose chronic HIV infection?
HIV serology: ELISA, western blot
during chronic infection, what is happening to the immune system?
slow relentless decline in CD4+ T cell count
what does HIV do to evade immune response?
mutates in process called viral escape
what is one key mechanism underlying disease pathogenesis?
chronic activation of the immune system. leads to decreased ability to control infection, promoges HIV rep in CD4+ t cells
what predicts the rate of progression to AIDS?
the HIV viral load set point that is established following acute infection
How is AIDS defined?
presence of one of 27 conditions indicative of severe immunodeciciency
HIV infection in person with a CD4+ count less than 200 cells/mm3 OR CD4+ T cell less than 15% of lymphocytes
What other infections are often seen with AIDS?
Kaposi’s sarcoma (associated with HHV-8)
Burkett’s lymphoma (asociated with EBV)
Cervical/anal cancers (assocd with HPV)
HIV infectd people are at risk for what other viral infections?
Hep B Hep C HSV CMV reactivated EBV (oral hairy leukoplasia)
The mutation rate of HIV means what for treatment?
it can mutate and become resistant to all known drug classes.
what does HAART stand for
highly active antiretroviral therapy
what does HAART consist of?
3 antiretroviral drugs of at least 2 different classes. (class = mechanism of action)
what is immune reconstitution syndrome?
may occur in some patients after HAART is initiated. due to rapid expansion of CD4+ T cells that increase inflammatory response if there is a co-infection.
Nucleoside Reverse Transcriptase Inhibitors (nRTI). what do they look like? what do they do, biochemically?
They look like nucleosides, and they terminate the growing HIV DNA chain
Non-nucleoside Reverse Transcriptase Inhibitors (nnRTI). what do they look like, what is the mechanism of action?
do not look like nucleosides. mech: inhibit reverse transcriptase enzyme activity, block synthesis of HIV DNA
Protease Inhibitors. mechanism?
block the protease activity of HIV protease. therefore prevent production of infectious HIV virions
CCR5 antagonists. mechanism?
block HIV virion binding to co-receptor, CC5R. prevents HIV from infecting cells
Fusion inhibitors. mech?
interfere with formation of gp41 fusion complex. block fusion of viral envelope with the host cell plasma membrane. HIV fails to infect cells
Integrase inhibitors. mech?
block integrase, prevent integration of HIV proviral DNA. virus production cannot occur.
