Acute Infection: 

During this period the mucosa are the dominant site of infection. The gastointestinal tract and other mucosal tissues contain at steady state at least half of the body’s T cells. These T cells are predominantly CCR5+, and many of them are in an activated state. During acute HIV infection, the virus rapidly multiples and propagates in the lymphoid compoent of mucosal tissues, thereby profoundly affecting the immune system soon after infection. In macaques infected with SIV, intestinal CD4+ T cells are almost entirely depleted within three weeks after infection.

Chronic Phase of Infection:

During the actue phase and into the chronic phase of infection, the sites of HIV replication begin to include other peripheral lymphoid organs. High levels of HIV accumulate in lymph node follicular dendritic cells, which are of epitthelial origin and therefore ditinct from the dendritic cells of hematopoietic origin. The virus persists mainly as a latent reservoir in memory CD4+% (CD45RO+) cells which possess the inherent ability to survive for a rpolonged period of time.

Once inside the host cell, many factors can modify viral replication. Proinflammatory conditions enhance viral replicaiton in most cell types. CXCL8 (IL-8) is produced by most cell types in the brain, enhances HIV replication in macrophages and T cells, and is elevated in the CSF in patients with HIV assocaited demential. While multiple mechanisms of latency have been dientified, recent studies have further defined the role of COUP_TF interacting protein 2 (CTIP-2) which as previously shown to inhibit LTR transcription via histone deacetylate (HDAC) and histone methyltransferase (HMT) recruitment.  (Zink, “HIV life cycle, innate immunity, and autophagy in the central nervous system” Curr Opin HIV AIDS, 2014). 

Long-Term Nonpreogressors:

It is clear that there is a significant percentage (about 5%) of HIV infected people who do not experience progression of HIV disease and whose CD4+ T cell counts remain stable and within normal range for many eyars. There LTNP have low but ravirable degrees of virus trapping in lymph nodes, whereas virus expressing cells are only rarely seen. Levels of all virologic parameters, including plasma viremia, viral burden (i.e., frequency of mononuclear cells containing HIV DNA) and virus expression are lower (20-40 fold) compared to progressors. However, HIV was generally isolated by coculturing lymph node mononuclear cells with PHA activated mononuclear cells from normal donors, indicating that the virus in most LTNP is replication competent and infectious.

Authophage is an important cellular mechniams that provides qulity control of proteins and eliiminating defective odler intracellular organelles. This is accompolished by the creation of autophagosomes, which consist of double membrane bodies that form within the cytoplasm and engulf cytoplasmic constiuents such as sub-cellular organelles and microbial pathogens, including viruses, and target them for degradation by fusion with a lysosome. There is evdience supporting autophagy as an important player in the host’s innat defense against HIV pathogenesis. PBMC form HIV-infected long term non-rogressors were shown to have significantly higher numbers of autophagic vesicles and higher levels of autophagic markers than normal progressors. (Zink, “HIV life cycle, innate immunity, and autophagy in the central nervous system” Curr Opin HIV AIDS, 2014)