HIV infection en route to endogenization: two cases

Abstract

The long-term spontaneous evolution of humans and the human immunodeficiency virus (HIV) is not well characterized; many vertebrate species, including humans, exhibit remnants of other retroviruses in their genomes that question such possible endogenization of HIV. We investigated two HIV-infected patients with no HIV-related disease and no detection with routine tests of plasma HIV RNA or cell-associated HIV DNA. We used Sanger and deep sequencing to retrieve HIV DNA sequences integrated in the human genome and tested the host humoral and cellular immune responses. We noticed that viruses from both patients were inactivated by the high prevalence of the transformation of tryptophan codons into stop codons (25% overall (3–100% per gene) and 24% overall (0–50% per gene)). In contrast, the humoral and/or cellular responses were strong for one patient and moderate for the other, indicating that a productive infection occurred at one stage of the infection. We speculate that the stimulation of APOBEC, the enzyme group that exchanges G for A in viral nucleic acids and is usually inhibited by the HIV protein Vif, has been amplified and made effective from the initial stage of the infection. Furthermore, we propose that a cure for HIV may occur through HIV endogenization in humans, as observed for many other retroviruses in mammals, rather than clearance of all traces of HIV from human cells, which defines viral eradication.

Dramatic HIV DNA degradation associated with spontaneous HIV suppression and disease-free outcome in a young seropositive woman following her infection

“…HIV-1 DNA Sanger population sequencing was performed as described previously 14 . All HIV genes were targeted by at least one PCR system (supplementary information), and all PCRs were conducted in quadruplicate.…”

“…We previously described two HIV-1-seropositive patients who we believe might have spontaneously cured of HIV 14,15 . Indeed, although they never received antiretrovirals, they persistently have a suppressed HIV replication, normal CD4 T cell counts, and no HIV-related disease for more than 10 years (one was HIV-diagnosed in 1985).…”

What viruses tell us about evolution and immunity: beyond Darwin?

“…HIV has indeed been shown to be able to infect germline cells, which would be a requirement for endogenization into the germline . In addition, there is evidence that defective HIV proviruses protect human T cells from superinfection with HIV …”

“…78,79 In addition, there is evidence that defective HIV proviruses protect human T cells from superinfection with HIV. 80 During evolution, retroviral endogenization happened frequently enough to populate the human genome with 450,000 retroviral elements that have typically accumulated inactivating mutations if the expression of viral genes was not selected for. The human genome consists of almost 50% of fulllength or truncated endogenous retroviruses and related retroelements.…”

From ‘purging’ to ‘endogenization’ of the HIV genome: a new approach to HIV eradication?

“…In this context, the paper by Didier Raoult's group published in this issue of CMI (5) represents an interesting and challenging approach to the topic. It is a radical change resulting from the use of advanced molecular techniques.…”