HIV infections

  • Article
    | Open Access

    The V3-crown of the HIV-1 envelope protein largely elicits non-neutralizing antibodies. Here, the authors show that the V3-crown can be targeted by broadly neutralizing designed ankyrin repeat proteins recognizing two conformations one of which resembles CCR5- bound V3.

    • Nikolas Friedrich
    • , Emanuel Stiegeler
    •  & Alexandra Trkola
  • Article
    | Open Access

    m6Am is a modification of the 5′ end of mRNAs catalyzed by PCIF1. Here, Zhang et al. show that HIV infection induces a decrease in m6Am of cellular mRNAs through Vpr-mediated PCIF1 ubiquitination and degradation, resulting in increased HIV replication through regulation of host transcription factors.

    • Qiong Zhang
    • , Yuqi Kang
    •  & Tariq M. Rana
  • Article
    | Open Access

    Antiretroviral therapy (ART) for the treatment of HIV-1 requires life-long daily adherence to supress viral replication, and nucleoside reverse transcriptase inhibitors that are commonly used in ART have not been converted into long-acting agents. Here, the authors report two lipophilic tenofovir (TVF) ProTide nanoformulations, NM1TFV and NM2TFV, which sustain drug levels above therapeutic concentrations for two months after a single intramuscular dose in rats.

    • Denise A. Cobb
    • , Nathan Smith
    •  & Benson Edagwa
  • Article
    | Open Access

    Anti-retroviral treatment does not fully resolve mucosal dysfunction and systemic inflammation in HIV infected individuals. Authors show here that an unusual population of regulatory T cells, distinguished by Amphiregulin expression and the incapability to suppress CD4 T cells might contribute to disrupted oral immune protection in HIV patients.

    • N. Bhaskaran
    • , E. Schneider
    •  & P. Pandiyan
  • Article
    | Open Access

    Current HIV cure-focused clinical trials rely on analytic treatment interruption (ATI) to evaluate post-treatment control (PTC). Here, combining untargetted metabolomics and glycomics in two HIV clinical cohorts, in vitro assays, and machine learning, the authors identify and validate metabolic and glycomic biomarkers linked to inflammatory pathways and HIV latency reactivation associated with PTC, suggesting non-invasive biomarkers as an alternative to predict HIV remission.

    • Leila B. Giron
    • , Clovis S. Palmer
    •  & Mohamed Abdel-Mohsen
  • Article
    | Open Access

    To provide in depth characterization of HIV reservoir cells, the authors here develop a single-cell approach to simultaneously sequence TCR, integration sites and proviral genomes, called STIP-Seq, and show that the translation-competent reservoir mainly consists of proviruses with short deletions at the 5’-end of the genome.

    • Basiel Cole
    • , Laurens Lambrechts
    •  & Linos Vandekerckhove
  • Article
    | Open Access

    CCR5 is a co-receptor for many transmitted HIV strains. Here, the authors show that biweekly injection of the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of a CCR5-tropic SHIV.

    • Xiao L. Chang
    • , Gabriela M. Webb
    •  & Jonah B. Sacha
  • Article
    | Open Access

    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.

    • Justin Harper
    • , Nicolas Huot
    •  & Mirko Paiardini
  • Article
    | Open Access

    Epithelial tissue mononuclear phagocytes (MNP) can transmit HIV to CD4 T cells, but less is known about sub-epithelial cells. Here, the authors describe MNPs in human anogenital and colorectal tissues and find that CD14+CD1c+ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 preferentially take up and transmit HIV.

    • Jake W. Rhodes
    • , Rachel A. Botting
    •  & Andrew N. Harman
  • Article
    | Open Access

    It is unknown whether capsulized fecal microbiota transplantation (FMT) can modify the microbiota of people with HIV. Here, the authors report the results of a pilot double-blind study, where 30 HIV-infected subjects on ART were randomized to either weekly oral FMT capsules or placebo for 8 weeks, and show that transplanted microbiota successfully engrafts and is able to attenuate HIV-associated dysbiosis.

    • Sergio Serrano-Villar
    • , Alba Talavera-Rodríguez
    •  & Santiago Moreno
  • Article
    | Open Access

    The intact proviral DNA assay quantifies the genomically intact HIV reservoir, but assay failure due to HIV-1 polymorphism has been observed. Here, the authors report a 28% failure rate in a cohort of people with HIV-1, and note within-host HIV-1 diversity as a further challenge to IPDA accuracy.

    • Natalie N. Kinloch
    • , Yanqin Ren
    •  & R. Brad Jones
  • Article
    | Open Access

    Removal of integrated HIV DNA remains a roadblock for HIV cure. Here, Mancuso et al. show that intravenous administration of an adeno-associated virus-based CRISPR/Cas9 gene editing construct to SIV-infected macaques results in excision of integrated proviral DNA from infected blood cells and tissues known to be viral reservoirs.

    • Pietro Mancuso
    • , Chen Chen
    •  & Kamel Khalili
  • Article
    | Open Access

    A vaccine to generate durable HIV broadly neutralizing antibodies (bnAb) from engineered B cells holds promise as an HIV functional cure. Here, the authors show that CRISPR/Cas-modified B cells expressing bnAbs as functional antigen receptors can be immunized to generate long-lived, germinal centre matured bnAb memory and plasma cells in mice.

    • Deli Huang
    • , Jenny Tuyet Tran
    •  & James E. Voss
  • Article
    | Open Access

    The HIV reservoir is a major hurdle for a cure of HIV, but the factors determining its size and dynamics remain unclear. Here the authors show in a large cohort of 610 HIV-1 infected individuals, who are on suppressive ART for a median of 5.4 years, that viral genetic factors contribute substantially to the HIV-1 reservoir size.

    • Chenjie Wan
    • , Nadine Bachmann
    •  & Sabine Yerly
  • Article
    | Open Access

    The cause of clonal expansions in the HIV reservoir remains unclear. Here, Gantner et al. perform single-cell TCR sequencing on longitudinal samples from eight individuals on antiretroviral therapy and find that antigens inducing clonal expansions of memory cells are major contributors to the HIV reservoir.

    • Pierre Gantner
    • , Amélie Pagliuzza
    •  & Nicolas Chomont
  • Article
    | Open Access

    The latent human immunodeficiency virus (HIV) reservoir in patients poses a problem for HIV cure. Here, Li et al. show that a combination of compounds inducing viral reactivation and cell death, inhibiting autophagy and blocking new infections can eliminate HIV infection in 50% of humanized HIV infected mice and in blood samples from infected patients.

    • Min Li
    • , Wei Liu
    •  & Jin Wang
  • Article
    | Open Access

    The role of sexual practice in HIV-associated gut microbiota remains poorly understood. Here, in a cohort of chronically treated HIV-infected people, the authors show microbiome signatures to be independent of sex and sexual practice and that the extent of dysbiosis correlates with nadir CD4, inflammatory markers, and comorbidities.

    • I. Vujkovic-Cvijin
    • , O. Sortino
    •  & I. Sereti
  • Article
    | Open Access

    Sex differences in the immune response to vaccines and infections have been well described in children and adults. Here the authors describe, in a cohort of 177 HIV-infected infants, innate immune sex differences in fetal life that increase female susceptibility to intrauterine HIV infection and increase the chances of subsequent HIV remission in infected males.

    • Emily Adland
    • , Jane Millar
    •  & Philip Goulder
  • Article
    | Open Access

    HIV prevalence varies throughout Africa, but the contribution of migration remains unclear. Using population-based data from ~22,000 persons, Grabowski et al. show that HIV-positive migrants selectively migrate to high prevalence areas and that out-migrants from these areas geographically disperse.

    • Mary Kate Grabowski
    • , Justin Lessler
    •  & Ronald H. Gray
  • Article
    | Open Access

    Elucidation of broadly neutralizing antibodies (bnAb) is a goal in HIV vaccine development. Here, Bradley et al. show that administration of CTLA-4 blocking antibody with vaccine antigens increases HIV-1 envelope antibody responses in macaques and a bnAb precursor mouse model.

    • Todd Bradley
    • , Masayuki Kuraoka
    •  & Barton F. Haynes
  • Article
    | Open Access

    HIV incidence among sex workers remains high in many settings. Here, the authors utilize individual-level data across ten countries in sub-Saharan Africa and suggest that increasingly punitive and non-protective laws are associated with HIV, and that stigmas and sex work laws may operate jointly in increasing HIV risk.

    • Carrie E. Lyons
    • , Sheree R. Schwartz
    •  & Stefan Baral
  • Article
    | Open Access

    Here, using cryo-EM and smFRET, Henderson et al. show how tryptophan 571 in the HIV-1 Env acts as a conformational switch during receptor-mediated viral entry and design HIV-1 Env proteins that cannot undergo conformational changes. This has important implications for HIV-1 vaccine design.

    • Rory Henderson
    • , Maolin Lu
    •  & S. Munir Alam
  • Article
    | Open Access

    Here, the authors use a molecular epidemiological approach to investigate the frequency and intensity of clustering of HIV with different set-point viral loads and find that frequently transmitted strains in genetic transmission clusters have significantly higher viral loads than nonclustered viruses.

    • Joel O. Wertheim
    • , Alexandra M. Oster
    •  & Walid Heneine
  • Article
    | Open Access

    Lactobacillus associates with vaginal protection from HIV-1 infection. Here, the authors show that lactobacilli extracellular vesicles contain bacterial proteins and metabolites that inhibit HIV-1 infection in T cells and in human cervico-vaginal and tonsillar tissues ex vivo via altering viral Env proteins.

    • Rogers A. Ñahui Palomino
    • , Christophe Vanpouille
    •  & Leonid Margolis
  • Article
    | Open Access

    Here, the authors investigate the outcome of prevention services scale-up on HIV incidence in a South African large population-based HIV surveillance cohort with over a decade of follow-up and associate a 43% reduction in incidence to earlier male medical circumcision and increased levels of antiretroviral therapy coverage.

    • Alain Vandormael
    • , Adam Akullian
    •  & Frank Tanser
  • Article
    | Open Access

    Here, the authors identify a broadly neutralizing antibody from an HIV-infected person that recognizes the membrane-proximal external region (MPER) of HIV envelope glycoprotein (Env) and has a short CDRH3 and low polyreactivity. Structural analysis shows how the antibody binds the MPER and Env on the viral membrane.

    • Lei Zhang
    • , Adriana Irimia
    •  & Michael B. Zwick
  • Article
    | Open Access

    Cervicovaginal inflammation and human papillomavirus (HPV) are separately associated with increased risk of HIV acquisition. Here the authors longitudinally profile 48 cervicovaginal cytokines and HPV status in a large observational HIV high-risk cohort, and show the same cytokines associate with HPV infection and HIV risk.

    • Lenine J. P. Liebenberg
    • , Lyle R. McKinnon
    •  & Quarraisha Abdool Karim
  • Article
    | Open Access

    Using cervical explant models and cervical tissue from ART-suppressed HIV+ women, the authors here show that resident memory T cells (TRM) in the cervical mucosa are preferentially infected and harbor more viral DNA, RNA and protein than non-TRM, suggesting that TRM may serve as viral reservoir in the cervical mucosa.

    • Jon Cantero-Pérez
    • , Judith Grau-Expósito
    •  & Meritxell Genescà
  • Article
    | Open Access

    High frequency semen exposure has been associated with activation of anti-HIV mechanisms in HIV negative sex workers. Here, Abdulhaqq et al. show that repeated vaginal exposure to semen reduces vaginal infection by SIV in non-human primates, and is associated with lower CCR5 expression in CD4 T-cells and a local type-I interferon response.

    • Shaheed A. Abdulhaqq
    • , Melween Martinez
    •  & Luis J. Montaner
  • Article
    | Open Access

    Various host factors may impact within-host pathogen evolution. Here, the authors develop a Bayesian approach for identifying host-pathogen interactions using large data sets of pathogen diversity, and apply it to investigate HLA-induced selection in the HIV-1 genome.

    • Duncan S. Palmer
    • , Isaac Turner
    •  & Gil McVean
  • Article
    | Open Access

    Here, the authors show that sequential treatment with long-acting slow-effective release ART and AAV9- based delivery of CRISPR-Cas9 results in undetectable levels of virus and integrated DNA in a subset of humanized HIV-1 infected mice. This proof-of-concept study suggests that HIV-1 elimination is possible.

    • Prasanta K. Dash
    • , Rafal Kaminski
    •  & Howard E. Gendelman
  • Article
    | Open Access

    Composition and function of immune populations at barrier surfaces is crucial for response to infection. Here, the authors identify a population of dendritic cells in human epidermis, abundant in anogenital epithelia and distinct from Langerhans cells by surface phenotype and by high capacity for HIV infection and transmission.

    • Kirstie M. Bertram
    • , Rachel A. Botting
    •  & Andrew N. Harman
  • Article
    | Open Access

    Stabilized, native-like trimers of the HIV envelope protein, such as SOSIP trimers, are potential antigens for an HIV vaccine. Here, the authors generate a SOSIP trimer based on the consensus sequence of group M isolates, determine its structure and exposure of common epitopes, and show immunogenicity in rabbits and non-human primates.

    • Kwinten Sliepen
    • , Byung Woo Han
    •  & Rogier W. Sanders
  • Article
    | Open Access

    Schistosoma mansoniinfection has been linked with an increased risk of HIV acquisition in women. Here, the authors show that standard S. mansoniinfection treatment causes a reduction of HIV entry into cervical and blood CD4+ T cells, which is sustained for up to two months and is associated with de-repression of IFN-I signaling. 

    • Sergey Yegorov
    • , Vineet Joag
    •  & Rupert Kaul
  • Article
    | Open Access

    Viral rebound following discontinuation of antiretroviral therapy (ART) is a major obstacle for HIV cure. Here, the authors show that adoptive cellular therapy using autologous Env-specific T cells augmented by therapeutic vaccination can control viral rebound after ART interruption in a SHIV macaque model.

    • Jin Fan
    • , Hua Liang
    •  & Yiming Shao
  • Article
    | Open Access

    Development of broadly neutralizing antibodies (bnAb) against HIV-1 in infected adults is a multi-step process unachievable by current vaccine approaches. Here the authors reconstruct the ontogeny of an infant bnAb, which develops in fewer steps, and identify its unique features that may shorten the path to HIV vaccines.

    • Cassandra A. Simonich
    • , Laura Doepker
    •  & Julie Overbaugh
  • Article
    | Open Access

    Here, using an integrative experimental and computational approach, Imle et al. show how cell motility and density affect HIV cell-associated transmission in a three-dimensional tissue-like culture system of CD4+ T cells and collagen, and how different collagen matrices restrict infection by cell-free virions.

    • Andrea Imle
    • , Peter Kumberger
    •  & Oliver T. Fackler
  • Article
    | Open Access

    Here, using the EcoHIV mouse model of infection, Bertrand et al. report that HIV infection contributes to ischemic stroke damage and decreased tissue recovery by disrupting blood–brain barrier integrity and show that antivirals with high CNS penetration can reduce tissue injury and accelerate post-stroke recovery.

    • Luc Bertrand
    • , Fannie Méroth
    •  & Michal Toborek
  • Article
    | Open Access

    Long-acting formulation of the integrase inhibitor cabotegravir (CAB LA) is in clinical development for HIV pre-exposure prophylaxis (PrEP). Here, using a SHIV macaque model, the authors show emergence of integrase mutations associated to CAB LA PrEP that confer pan-integrase inhibitor resistance.

    • Jessica Radzio-Basu
    • , Olivia Council
    •  & J. Gerardo García-Lerma
  • Article
    | Open Access

    Here, the authors present the structure of the HIV envelope (Env) protein from a transmitted founder virus and show that, while the overall structure of the Env trimer is similar to other closed trimers, the fusion peptide is buried in the hydrophobic core of the trimer, which is similar to open state trimers.

    • Neeti Ananthaswamy
    • , Qianglin Fang
    •  & Venigalla B. Rao
  • Article
    | Open Access

    Oral vaccination is a potential option to elicit systemic and mucosal immunity against HIV. Here, Jones et al. show that oral vaccination with a modified needle-free injector induces protective immunity against SHIV in non-human primates and is superior to topical application of vaccines to oral tissues.

    • Andrew T. Jones
    • , Xiaoying Shen
    •  & Rama Rao Amara
  • Article
    | Open Access

    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.

    • Rémi Fromentin
    • , Sandrina DaFonseca
    •  & Nicolas Chomont