This news just came fresh. Researchers from the University of Montpellier reported that they discovered something huge (Descours et al., 2017) and it is about the infamous HIV.
HIV is ridiculously notorious because it can survive well by being latent in CD4 T cells. While it is being latent, it does not express its proteins, therefore it is not actively undergoing viral replication. Here is what makes it difficult: if there is no circulating HIV because it is being latent, it is virtually impossible to see it in a blood test. You might think sequencing CD4 T cells DNA to see for evidence of the integrated HIV DNA, but what’s your chance of bumping into CD4 T cells that have been infested with the HIV?
It is a logical step that you look for changes in the CD4 T cells gene expression. Descours and colleagues did series of experiments and their data suggests that about 103 genes are upregulated that are specific for latently HIV-infected cells. Of those 103 genes, 16 of them (~15%) code for transmembrane proteins. Why we care about transmembrane proteins? Well, because it is stuck on the latently infected CD4 T cells the same way your limbs stuck to your trunk, it makes the latently infected CD4 T cells phenotypically identifiable. There is one transmembrane protein that really stands out: the CD32a receptor protein. Descours and colleagues found out that a subpopulation of CD4 T cells expressing CD32a receptor host up to three copies of HIV DNA per cell.
From this paper I learned something new: resting CD4 T cells are non-permissive to HIV-1 infection but it supports HIV-1 viral persistency. It is because HIV can only infect CD4 T cells that are activated. It is generally assumed that a T cell (when it is active) it could be infected by HIV and then the cell recycles to a resting state, trapping the virus into latency (Chavez et al., 2015). So now we need to find that inactivated CD4 T cells. Descours’s work points out that latent HIV in an inactivated CD4 T cell can induce the expression of CD32a receptor protein.
This note is pretty much preliminary. I hope I could this paper thoroughly soon. I hope I could find an online discussion regarding this paper so that I could learn more about the work, assumptions, and further implications from this data.
- Descours et al., 2017, Nature 543(7647):564-567, doi:10.1038/nature21710
- Chavez et al., 2015, PLOS Pathogens 11(6):e1004955 doi:10.1371/journal.ppat.1004955