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Viral and CD4+ T cells in HIV infection

6 important questions on Viral and CD4+ T cells in HIV infection

What is the hallmark of an HIV-1 infection regarding the immune system? Why is this a problem if you are infected?

CD4+ T cell decline is the hallmark which leads to loss of CD4+ T cells which causes AIDS. HIV infects CD4+ T cells, when losing CD4 T cells you lose the adaptive immunity response due to the central role of these cells --> required for CD8 cells activation

Is the HIV virus latent? If not, why is it still a problem?

No, because research showed when production was inhibited, a steady continuous decline of viral loss was seen, which gave a decrease in the slope and a half time of 2 days of the virus. This gave rise to mutants through fast replication, meaning the virus is not latent. This leads to large implications for HIV evolution, escape from anti-virals and from the immune response, basis for combination treatment.

The main problem now is the during treatment the level on virions is kept low, but the patients will keep a latent level of infected cells.

Why can't HIV-induced cytopathicity be a cause of CD4+ T cell loss? (pathological changes in cells)

Because the number of apoptotic cells is higher than the number of infected cells. Also most apoptotic cells are CD8+ T cells and only a few infected cells undergo apoptosis (and few apoptotic cells were infected).

Telomere shortening can be seen as a marker of replicative history of T cells (also associated with cell senescence). Then why is it weird that naive and memory T cell telomeric length decline parallel? And are CD4+ T cell telomeres shortening more rapidly than the HIV infection is dividing?

Memory T cells divide much more rapidly than naïve cells.

No, CD8+ T cells showed stronger telomeric loss but not CD4+ T cells. Therefore telomeric length can't be used as marker for loss of CD4+ T cells in HIV infections, thus is not the cause of this loss.

How can the thymic output be measured? What was seen for this in and HIV infection?

By measuring the TREC content (come from V(D)J rearrangement). The TREC content decline with age has been interpretated to reflect thymus decline --> TREC decline in HIV infection looks like individuals lost their thymus 20 years ago. The TREC concent only declines when the naive T-cell numbers decline, so would be a good measurement, however proliferation strongly influences TREC contents but not the thymic ouput.

At the moment what seems to be the cause for CD4+ T ceell loss with an HIV infection and how does this work?

Increased CD4+ T cell activation, thus chronic immune activation is the problem. The immune system is not trying to compensate for the loss of CD4+ T cells, because division is driven by the virus. Increased T cell division in HIV-1 infection is not a
homeostatic response to T cell depletion, but reflects persistent activation of the immune system
High immune response leads to AIDS state (high level of CD70)