Altered dynamics and differential infection profiles of lymphoid and myeloid cell subsets during acute and chronic HIV-1 infection

Abstract

The dynamics of immune cell populations during acute HIV-1 infection are not fully deciphered, especially for non-T cells. In this study, we tested whether specific cellular subsets of the innate arm of the immune response are affected early after HIV-1 infection. Using a cohort of HIV-1-infected individuals, we have monitored the relative frequency of blood T lymphocytes, monocytes, and DCs at various infection stages and measured their respective intracellular HIV-1 DNA loads. The HIV-1 DNA load in naive CD4(+) T lymphocytes, which are lost very early during acute infection, was ten- to 100-fold lower than in CD57(-) and CD57(+) memory CD4(+) T lymphocytes. We observed that despite rapid, persistent loss after HIV-1 infection, pDCs represented a non-negligible HIV-1 DNA reservoir. CD16(+) proinflammatory cDCs and monocytes accumulated gradually, and HIV-infected CD16(+) monocytes contained higher HIV-1 DNA loads than their CD16(-) counterpart during acute infection. During chronic infection, CD16(+) cDCs exhibited higher HIV-1 DNA loads than the CD16(-) population. Overall, our results demonstrate that non-T cell compartments are a major HIV-1 DNA reservoir, and CD16(+) monocytes and CD16(+) cDCs potentially play an important role in HIV-1 dissemination.

HIV-Infected Dendritic Cells Present Endogenous MHC Class II–Restricted Antigens to HIV-Specific CD4+ T Cells

“…Although most HIV particles are rapidly degraded upon their encounter with a DC (34,35), providing material for MHC-II Ag presentation (32,36,37), some viral particles escape degradation and are either directly transmitted to CD4 + T cells by trans-infection or initiate cis-infection of DC. Indeed, in the absence of treatment, infected DC can be found in the blood of HIV + donors (38)(39)(40) and, ex vivo, sorted BCDA1 + myeloid DC support productive infection of HIV-1 (41,42). Monocyte-derived DC are also equipped with HIV receptors (CD4, CCR5, and CXCR4) allowing cis-infection (35,(43)(44)(45).…”

Establishment and Reversal of HIV-1 Latency in Naive and Central Memory CD4+T CellsIn Vitro

“…This finding indicates that quantification of viral DNA alone is not necessarily predictive of the size of the inducible latent reservoir and suggests caution in labeling a cellular reservoir of latent HIV-1 as "major" based solely on the frequency of infection. In addition to the memory CD4 ϩ T cell subsets, HIV-1 DNA is almost always detected in T N cells in both viremic and suppressed individuals, although with a much lower frequency than in the T CM and T TM compartments (6,7,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Interestingly, in 2013 Saez-Cirion et al reported that in some HIV-1-infected individuals who received ART within 10 weeks of primary infection, viremia could be controlled for at least 24 months posttreatment interruption (8).…”

HIV-1 transcriptional activity during frequent longitudinal sampling in aviremic patients on antiretroviral therapy

“…Of all the tested variables, only nadir CD4 þ showed a significant (negative) correlation to CA-US HIV-1 RNA (r ¼ À0.465, P ¼ 0.017) which could reflect a functional defect in the cellular immune response in individuals with low nadir CD4 þ due to lack of immunological recovery. Since the latently infected cells are mainly within the CD4 þ T-memory subsets and the proportions of naive CD4 þ T cells vs. memory CD4 þ T cells varies between HIV-infected individuals, we adjusted all measures for the proportion of naïve T cells [12,[54][55][56][57]. This correlation remained significant when adjusted for the relative contribution of T N at baseline (r ¼ À0.477, P ¼ 0.014).…”