HIV virology and immunology Flashcards
What type of virus is HIV?
HIV is a retrovirus, an RNA virus which uses reverse transcriptase (RT) to make a DNA copy that becomes integrated into the DNA of the infected cell
Why can HIV-1 evolve rapidly?
- Error-prone replication (the enzyme reverse transcriptase makes at least 1 error in every replication cycle)
- Allows there to be an archive to versions that could be resistant to antibiotics
- Rapid viral replication (generation time ~2.5 days)
- Large population sizes (~1010 new virus particles produced each day)
What is defined as AIDS?
CD4 < 200
What is the key features of pathogenesis for HIV?
- HIV is integrated into the DNA of the infected CD4-expressing cells
- HIV infects a range of CD4 + immune cells in addition to helper T-cells
How does HIV infect other cells?
HIV can pass directly from cell to cell, and so it is relatively inaccessible to antibodies in the blood
Describe immune activation in HIV
- Early in HIV infection, there is a dramatic loss of CD4+ T-cells in the lymphoid tissue in the gut
- this increases gut mucosal permeability, allowing passage of bacterial products, such as LPS
- These bacterial products stimulate circulating immune cells (particularly monocytes), setting up a cycle of chronic immune activation that ultimately exhausts the immune system
- Persistent activation predisposes immune cells to cell death and intense proliferation cycles that result in impaired function and exhaustion
Why does the immune response to HIV-1 fail to clear the virus?
- Antibodies develop against most viral proteins, but neutralising antibodies take months to develop and rarely neutralise the primary HIV strains that are transmitted from person to person
- One of the key immune responses to HIV-1, from CD4+ T-helper cells, is lost from very early in infection, because these are the cells HIV infects first
- There is a very vigorous response from cytotoxic CD8+ T-cells, which provides the major force controlling viral replication but ultimately fail when “immune exhaustion” sets in
What are the steps in HIV replication?
- Attachment
- Entry
- Uncoating
- Reverse transcription
- Genome integration
- Transcription of viral RNA
- Splicing of mRNA and translation into proteins
- Assembly of new virions
- Budding
What proteins are present on HIV envelopes?
gp120/41
How does HIV bind to receptors?
- HIV infects cells that express CD4 and the interaction between CD4 and gp120 is conserved among all primate lentiviruses
- Binding of gp120 to CD4 induces a conformational change in gp120
- The co-receptor binding site includes a conserved bridging sheet and also amino acids in the V3 loop
Which cells do HIV replicate in?
in CD4 positive cell
Why do do most HIV-1-infected people fail to make an effective antibody response?
- The HIV-1 envelope spike is heavily glycosylated (with sugars resembling human types), which makes it difficult for antibodies to bind to the surface
What can gp120/41 proteins do?
- can change substantially without affecting virus function
- Thus the virus can evolve very quickly to avoid antibody recognition (including by the addition of more sugar molecules)
Describe features of a ‘functional’ HIV cure
- Absence of viral replication off antiretroviral therapy: plasma viral load remains below detection
- Latently infected cells persist (detectable viral DNA) but minimal evidence of viral replication
- No CD4 count decline
- No risk of onward transmission (presumably)
- Seen in “elite controllers” and “post-treatment” controllers (treated early in primary HIV infection)
