If I were to plan an experiment to deduce whether or not PD-1 is absolutely necessary for HIV to establish latent infection in CD4 memory cells, how would I go about doing this?
More specifically:
Would the approach of incubating HIV particles with either a) WT CD4 memory cells or b) PD-1 negative CD4 memory cells be sufficient? I understand that I would have to define which subset I was focusing on, given the heterogeneity of these cells.
What is the appropriate source of memory cells? i.e, extracting memory cells from a human and then deleting PD-1 vs. using some sort of CD4 memory cell line.
Is proviral integration a sufficient marker of latency?
It's refers to the type of cell that the human immunodeficiency virus (HIV) infects and replicates in. HIV infects human immune system cells such as T cells (specifically CD4+ T helper cells), macrophages, and dendritic cells.
Entry of HIV-1 to macrophages and T helper cells, is mediated not only through interaction of the virion envelope glycoproteins with the CD4 molecule on the target cells but also with its co-receptors.
Macrophage (M-tropic) strains of HIV-1, or non-syncitia-inducing strains (NSI) use CCR5 receptor for entry and are thus able to replicate in macrophages and CD4+ T-cells. These strains are now called R5 viruses.
T-tropic strains, or syncitia-inducing (SI) strains replicate CD4+ T-cells as well as in macrophages and use the CXCR4 receptor for entry. These strains are now called X4 viruses.
Dual-tropic HIV-1 strains: A strain of HIV that can enter and infect a host CD4 cell by attach to a CD4 receptor, then attach to either the CCR5 or CXCR4 coreceptor on the CD4 T lymphocyte and finally fuse its membrane with the CD4 cell membrane. HIV is usually R5-tropic (uses CCR5) during the early stages of infection, but the virus may later switch to using either only CXCR4 (X4-tropic) or both CCR5 and CXCR4 (dual-tropic).
Viruses that use only the CCR5 receptor are termed R5, those that only use CXCR4 are termed X4, and those that use both, X4R5.