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Resting T cells are difficult to manipulate, and are a reservoir for latent HIV. Here, the authors develop a lipid nanoparticle formulation with the ability to transfect resting primary human T cells, enabling delivery of mRNAs that result in reactivation of latent HIV. This could help development of HIV cure strategies.

Production of reactive oxygen species is an ancient antimicrobial mechanism, but its role in antiviral defense in mammals is unclear. Here, To et al. show that virus infection activates endosomal NOX2 oxidase and restricts TLR7 signaling, and that an endosomal NOX2 inhibitor decreases viral pathogenicity.

Cas13b can be harnessed to target and degrade RNA transcripts inside a cellular environment. Here the authors reprogram Cas13b to target SARSCoV-2 transcripts in infected mammalian cells and reveal its resilience to variants thanks to single mismatch tolerance.

The ‘Strategies for an HIV Cure’ conference was held 27–28 April 2018 in Beijing, China, and was hosted by The People's Republic of China Ministry of Science and Technology and the Chinese Academy of Sciences.

Antiviral drugs prevent HIV from replicating, but the virus can hide in the cells of infected individuals in a non-replicating, latent form. A two-pronged approach to target this latent virus shows promise in monkeys.

The impact of COVID-19 vaccination on post-COVID conditions is not well understood. Here, the authors use electronic health record data from a network of eight integrated healthcare systems in the United States to compare rates of post-COVID conditions in those with and without vaccination.

The development of effective antiretroviral therapies has greatly improved the disease prognosis for patients with HIV. However, the limitations of these therapies have renewed interest in developing alternative treatment strategies. Here, a group of experts from the International AIDS Society discuss the research steps that need to be taken to achieve the ultimate objective — a cure for HIV.

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.

In people with HIV-1 undergoing antiretroviral treatment interruption, lefitolimod combined with broadly neutralizing antibodies (bNAbs) did not delay viral rebound beyond that achieved with bNAbs alone, raising the question of how to optimize combination immunotherapy to control HIV-1.

The immune checkpoint molecule PD-1 is expressed on a fraction of CD4⁺ T cells latently infected with HIV, but whether PD-1 plays a functional role in reservoir persistence remains unknown. Here, Fromentin et al. show that PD-1 blockade potentiates latency reversal ex vivo in CD4⁺ T cells from ART suppressed individuals.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Treatment of HIV-1 infected patients with latency-reversing agents (LRA) induces transcription of proviruses in CD4 T cells. Using single-genome sequencing, the authors show that the LRA-induced CD4 T cell-associated HIV RNA is genetically diverse and contains a high proportion of defective RNA.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Analysis of the whole-genome transcriptional activity of HIV-specific CD4⁺ T cells demonstrates distinct profiles associated with natural control of HIV replication, as well as dysfunctional phenotypes that persist even after effective antiretroviral therapy.

B cells and follicular helper T cells in B cell follicles can act as important reservoirs for chronic infection by viruses such as HIV or EBV. Yu and colleagues show that a specialized subpopulation of cytotoxic T cells can enter the B cell follicles to eliminate such virus-infected cells.

Gene discovery and polygenic predictions from a genome-wide association study of educational attainment in 1.1 million individuals.

In HIV infection, the virus invades and destroys the immune system of the host. This Primer by Bekker and colleagues summarizes the epidemiology, mechanisms, diagnosis and treatment of HIV infection, and discusses patient quality of life and open research questions for this condition.

Recent clinical trials have shown that blocking immune checkpoint molecules can boost antitumour immune responses. In this Review, the authors consider whether targeting these pathways could also be used to combat a range of infectious diseases, such as malaria, tuberculosis and chronic viral infections.

In this Analysis, the authors discuss different strategies for the post-treatment control of HIV infection. They use mathematical modelling to predict the impact of different interventions and to estimate the therapeutic efficacy required to achieve a functional cure.

A genome-wide association study in 293,723 individuals identifies 74 genetic variants associated with educational attainment, which, although only explaining a small proportion of the variation in educational attainment, highlights candidate genes and pathways for further study.

The International AIDS Society Towards a Cure Working Group lays out its scientific strategy to achieve a cure for HIV.

Anecdotal reports of HIV-infected children who have continued to control viral replication after discontinuing antiretroviral therapy have led to the hope that unique factors associated with paediatric infection might offer greater potential for HIV cure in children than in adults.