Brain microglia (MG) may serve as a human immunodeficiency virus 1 (HIV) reservoir and ignite rebound viremia following cessation of antiretroviral therapy (ART), but they have yet to be proven to harbor replication-competent HIV. Here, we isolated brain myeloid cells (BrMCs) from nonhuman primates and rapid autopsy of people with HIV (PWH) on ART and sought evidence of persistent viral infection. BrMCs predominantly displayed microglial markers, in which up to 99.9% of the BrMCs were TMEM119⁺ MG. Total and integrated SIV or HIV DNA was detectable in the MG, with low levels of cell-associated viral RNA. Provirus in MG was highly sensitive to epigenetic inhibition. Outgrowth virus from parietal cortex MG in an individual with HIV productively infected both MG and PBMCs. This inducible, replication-competent virus and virus from basal ganglia proviral DNA were closely related but highly divergent from variants in peripheral compartments. Phenotyping studies characterized brain-derived virus as macrophage tropic based on the ability of the virus to infect cells expressing low levels of CD4. The lack of genetic diversity in virus from the brain suggests that this macrophage-tropic lineage quickly colonized brain regions. These data demonstrate that MG harbor replication-competent HIV and serve as a persistent reservoir in the brain.

Since the COVID-19 pandemic first hit Wuhan, China, in December 2019, scientists have been racing to develop and test novel vaccines to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The speed of scientific discovery related to COVID-19 is unprecedented. With several vaccine candidates already being tested in clinical trials, we pose the question: what will the vaccine hesitant do in the face of this pandemic?

Neutralizing antibodies prevent Zika infection in nonhuman primates.

Zika virus infection early after birth has deleterious effects on the developing brain and long-term behavioral changes in rhesus macaques.

While antiretroviral therapy (ART) can reduce HIV replication, the virus cannot be eradicated from an infected individual, and our incomplete understanding of HIV persistence in reservoirs greatly complicates the generation of a cure for HIV infection. Given the immaturity of the infant immune system, it is critically important to study HIV reservoirs specifically in this population. Here, we established a pediatric animal model to simulate breastfeeding transmission and study SIV reservoirs in rhesus macaque (RM) infants. Our study demonstrates that ART can be safely administered to infant RMs for prolonged periods and that it efficiently controls viral replication in this model. SIV persistence was shown in blood and tissues, with similar anatomic distributions of SIV reservoirs in infant and adult RMs. However, in the peripheral blood and lymph nodes, a greater contribution of the naive CD4 ⁺ T cells to the SIV reservoir was observed in infants than in adults.