The largest HIV-1-infected T cell clones in children on long-term combination antiretroviral therapy contain solo LTRs

Abstract

Combination antiretroviral therapy (cART) suppresses viral replication but does not cure HIV infection because a reservoir of infectious (intact) HIV proviruses persists in long-lived CD4+T cells. However, a large majority (>95%) of HIV-infected cells that persist on effective cART carry defective (non-infectious) proviruses. Defective proviruses consisting of only a single LTR (solo long terminal repeat) are commonly found as endogenous retroviruses in many animal species, but the frequency of solo-LTR HIV proviruses has not been well defined. Here we show that, in five pediatric donors whose viremia was suppressed on cART for at least 5 years, the proviruses in the nine largest clones of HIV-infected cells were solo LTRs. The sizes of five of these clones were assayed longitudinally by integration site-specific quantitative PCR. Minor waxing and waning of the clones was observed, suggesting that these clones are generally stable over time. Our findings show that solo LTRs comprise a large fraction of the proviruses in infected cell clones that persist in children on long-term cART. IMPORTANCE This work highlights that severely deleted HIV-1 proviruses comprise a significant proportion of the proviral landscape and are often overlooked.

Role of HIV-1 Tat Protein Interactions with Host Receptors in HIV Infection and Pathogenesis

“…Indeed, seroreversion of the antibody response to HIV, a bona fide proxy of virus remission or eradication, was reported in a small cohort of 23 women from Gabon infected with a Tat in which the cysteine in position 22 was replaced by a serine (Tat Oyi) making its transactivation silent [84]. Similarly, in the cART era, progressive accumulation over time of proviruses defective for replication [85] and/or for gene expression (i.e., containing solo LTRs) [86] was found. This is probably the result of the combined pressure exerted by cART and by a sufficiently restored immune response against HIV.…”

Assessment of pain-related behaviors in HIV-1 transgenic rats as a model of HIV-associated chronic pain

“…The proviruses are called “inactive” or “deffecive” since they have a mutation within the gene and therefore, were thought to be not related to the development of HIV-1 related pathogenesis. 15 Although cART inhibits viral replication, it does not address these proviruses. Recent findings indicate that the defective proviruses can be recognized by T lymphocytes and therefore, contribute to the increased inflammatory state and potentially pain.…”