Search

‘The induction and coordination of immune cells in response to SARS-CoV-2 infection are critical in the immunopathology of COVID-19. Here the authors use a rhesus macaque model of SARS-CoV-2 infection and show key populations of macrophage drive the inflammatory cytokine production in the alveolar space’.

Understanding the resistance of natural hosts of simian immunodeficiency virus (SIV)—such as sooty mangabeys—to disease progression may yield insights applicable to HIV-1. In this issue, Paiardini et al. report that CD4⁺ central memory T (T_CM) cells from sooty mangabeys do not strongly upregulate CCR5 upon activation and are more resistant to SIV infection than T_CM cells from rhesus macaques, which may contribute to proper immune control and prevention of disease in these natural hosts.

Paiardini and colleagues describe a subset of lymph node HIV- and SIV-specific TOX^hiTCF1⁺CD39⁺CD8⁺ T cells that coexhibit stem- and effector-like phenotypic and transcriptional profiles and associate with reduced viral burden.

Although antiretroviral therapy (ART) is able to successfully suppress plasma viremia in most people living with HIV, ART withdrawal typically results in viral replication and rebound. Authors investigate the effect, in terms of delay in viral replication, and immune cell dynamics in lymphoid tissue, of fingolimod (FTY720) administration at the time of ART initiation in SIV-infected rhesus macaques.

When monkeys are infected with a virus similar to HIV, treated with antiretroviral therapy (ART), and are administered a ‘combo therapy’ made of antibodies against molecules that inhibit immune responses, they control viral rebound when ART is discontinued for more than 6 months

Infection of African green monkeys with SIV is associated with reduced pathogenicity. Here the authors explore the requirement of differentiated NK cell populations in a pathogenic Rhesus macaque model of SIV infection and show administration of IL-21 and IFNα rescues terminally differentiated NK cells, similarly to what found in African green monkeys, and limits the SIV reservoir in antiretroviral therapy treated macaques.

Here the authors map the dynamics of human NK cell residency and recirculation, showing that CD56^bright NK cells transiently occupy tissues and recirculate via lymphatics, whereas CD56^dim NK cells remain vascular except during inflammation.

Depletion of CD8⁺ T cells before infection or early antiretroviral therapy initiation elucidates the role of cytotoxic T lymphocytes during formation of the latent simian immunodeficiency virus reservoir.

Reservoirs of virally infected cells that are resistant to standard antiretroviral therapy make HIV-1 infection an incurable disease. A new study shows that follicular T helper cells in lymph node germinal centers are prime niches for HIV-1 persistence during antiviral therapy.

NK cells control SIV infection in secondary lymphoid tissues in the natural host that typically doesn’t progress toward disease. Here the authors show that this control is associated with terminal NK cell differentiation and improved MHC-E-dependent activity lacking in pathogenic SIV infection.

Immune checkpoint blockade has been proposed as a potentially curative strategy to reduce the HIV reservoir. Studies in monkeys now show that this approach alone is ineffective at enabling viral control after antiretroviral treatment interruption.

The interleukin-15 superagonist N-803, combined with the depletion of CD8⁺ lymphocytes, induced a robust and persistent reactivation of the virus in vivo in both antiretroviral-therapy-treated SIV-infected macaques and HIV-infected humanized mice.

In this work, authors take a multiomics and microfluidics-based approach to elucidate the mechanism of endothelial damage in critical illness associated with SARS-CoV-2.

Innate lymphoid cells (ILCs) have been shown to be depleted during HIV-1 infection. Here the authors show that ILC loss is associated with CD4 depletion and gastrointestinal damage in a primate model of SIV infection.

A strategy for assessing the effectiveness of different strategies for HIV cure is presented.

HIV infection persists under antiretroviral therapy due to a reservoir of latently infected cells. This Perspective discusses how host immune responses might affect the establishment and persistence of the viral reservoir, an understanding of which supports the development of immune-based approaches to ‘cure’ HIV infection by disrupting the reservoir.

Whole-genome sequencing and comparative genomic analysis of immune-related genes of Cercocebus atys and Macaca mulatta identify candidate genes, such as ICAM2 and TLR4, that may explain the AIDS resistance of C. atys.

An effective and scalable cure strategy is a top priority for the HIV research field; this Review discusses recent advances, knowledge gaps, and priority research areas for the next 5 years.