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| Open AccessSelective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats
The ecology of Ebola virus (EBOV) is still largely unclear. Here, the authors show that Angolan freetailed bats are selectively permissive to EBOV infection, but not to other filoviruses, and demonstrate EBOV placental tissue tropism indicating potential horizontal and vertical transmission between conspecifics.
- S. A. Riesle-Sbarbaro
- , G. Wibbelt
- & A. Kurth
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Article
| Open AccessPotent latency reversal by Tat RNA-containing nanoparticle enables multi-omic analysis of the HIV-1 reservoir
Reactivating latent HIV reservoirs could be beneficial towards a functional cure. Here, the authors show that Tat-LNP effectively reactivates HIV while preserving the cell transcriptome. Upon reactivation, p24+ cells exhibit distinct genes and pathways potentially contributing to their persistence.
- Marion Pardons
- , Basiel Cole
- & Linos Vandekerckhove
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Article
| Open AccessPRMT2 promotes HIV-1 latency by preventing nucleolar exit and phase separation of Tat into the Super Elongation Complex
The mechanisms regulating Tat function for HIV-1 replication remain poorly understood. Here, the authors reveal that the transcriptional activity of Tat is modulated by a PRMT2-licensed switch between its nucleolar sequestration and phase separation into the nucleoplasmic Super Elongation Complex (SEC) droplets.
- Jiaxing Jin
- , Hui Bai
- & Deqing Hu
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Article
| Open AccessPanoramic analysis of coronaviruses carried by representative bat species in Southern China to better understand the coronavirus sphere
In this study, Han, Xu, and Wang et al. probe the diversity of bat coronaviruses (CoVs), revealing their evolutionary pattern with hosts. It underscores the evolutionary processes of CoVs, including SARS-CoV-2, and emphasizes the urgency of ongoing bat CoV surveillance.
- Yelin Han
- , Panpan Xu
- & Zhiqiang Wu
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Article
| Open AccessTwo point mutations in protocadherin-1 disrupt hantavirus recognition and afford protection against lethal infection
Protocadherin-1 (PCDH1) is a critical host factor for hantaviruses that can cause severe cardiopulmonary syndrome. Here, the authors map the binding site of the viral glycoprotein complex within PCDH1 and show that mutations engineered at this site can protect Syrian hamsters from viral challenge.
- Megan M. Slough
- , Rong Li
- & Kartik Chandran
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Article
| Open AccessTrispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections
One of the main hurdles to curing HIV infection are viral reservoirs. Here, the authors develop a trispecific antibody and demonstrate its ability to simultaneously activate and target latently HIV−1 infected cells for elimination by T cells as an alternative strategy for HIV cure.
- Wanwisa Promsote
- , Ling Xu
- & Richard A. Koup
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Article
| Open AccessPhenotypic characterization of single CD4+ T cells harboring genetically intact and inducible HIV genomes
Some HIV-infected cells persist during antiretroviral therapies (ART) but their phenotype is less clear. Dufour et al. show that HIV-infected cells that persist in people receiving ART are phenotypically diverse and that CD4+ T cells expressing the integrin VLA-4 are highly enriched in replication-competent HIV.
- Caroline Dufour
- , Corentin Richard
- & Nicolas Chomont
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Matters Arising
| Open AccessMachine-learning prediction of hosts of novel coronaviruses requires caution as it may affect wildlife conservation
- Sophie Lund Rasmussen
- , Cino Pertoldi
- & David W. Macdonald
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Matters Arising
| Open AccessReply to: Machine-learning prediction of hosts of novel coronaviruses requires caution as it may affect wildlife conservation
- Marcus S. C. Blagrove
- , Matthew Baylis
- & Maya Wardeh
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Article
| Open AccessTherapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques
Antiretroviral therapy alone is insufficient in curing HIV-1 infection, due to latent viral reservoir persistency. Here, authors explore the post-virologic control of combining active and passive immunisation with vesatolimod, in a SHIV-infected rhesus macaque model.
- Victoria E. K. Walker-Sperling
- , Noe B. Mercado
- & Dan H. Barouch
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Article
| Open AccessIsolation of infectious Lloviu virus from Schreiber’s bats in Hungary
Lloviu virus (LLOV) is a filovirus that was first identified in 2002 in Schreiber’s bats in Europe. Here, the authors isolate infectious LLOV from Schreiber’s bats in Hungary and show that it can infect human cells in vitro, suggesting potential for zoonotic events. They furthermore detect LLOV RNA in ectoparasites of sampled bats.
- Gábor Kemenesi
- , Gábor E. Tóth
- & Ferenc Jakab
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Article
| Open AccessLatency reversal plus natural killer cells diminish HIV reservoir in vivo
Here, Kim et al. describe a new kick and kill strategy utilizing a single administration of a protein kinase C modulator and latency reversing agent in combination with injections of allogeneic peripheral blood natural killer cells diminishes the HIV reservoir in HIV-infected humanized mice.
- Jocelyn T. Kim
- , Tian-Hao Zhang
- & Jerome A. Zack
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Article
| Open AccessA novel nairovirus associated with acute febrile illness in Hokkaido, Japan
Here, Kodama et al. describe the discovery, isolation and characterization of a novel tick-borne orthonairovirus, designated Yezo virus (YEZV), from patients with an acute febrile illness in Japan. Serological testing of wildlife and molecular screening of ticks suggest an endemic circulation of YEZV in Japan.
- Fumihiro Kodama
- , Hiroki Yamaguchi
- & Keita Matsuno
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Article
| Open AccessNon-invasive plasma glycomic and metabolic biomarkers of post-treatment control of HIV
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
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Article
| Open AccessIn-depth single-cell analysis of translation-competent HIV-1 reservoirs identifies cellular sources of plasma viremia
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
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Article
| Open AccessSelective cell death in HIV-1-infected cells by DDX3 inhibitors leads to depletion of the inducible reservoir
DEAD-box polypeptide 3 (DDX3) is a host protein belonging to the family of ATP-dependent RNA helicases. Here, the authors demonstrate that DDX3 inhibitors reverse HIV-1 latency and selectively induce cell death in HIV-1-infected cell lines, primary CD4+ T cells and in CD4+ T cells from cART-suppressed people living with HIV-1.
- Shringar Rao
- , Cynthia Lungu
- & Tokameh Mahmoudi
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Article
| Open AccessPersistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques
The existence of HIV reservoir and ongoing replication despite antiretroviral therapy (ART) represents a barrier for cure efforts. Here, using SIV/SHIV-infected rhesus macaque suppressed with ART for one year, the authors characterize multiple lymphoid and non-lymphoid tissues and show that while the viral reservoir exhibits a wide anatomic heterogeneity, persistent viral transcription is mainly restricted to secondary lymphoid organs.
- Anthony M. Cadena
- , John D. Ventura
- & Dan H. Barouch
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Article
| Open AccessPredicting mammalian hosts in which novel coronaviruses can be generated
Homologous recombination between co-infecting coronaviruses can produce novel pathogens. Here, Wardeh et al. develop a machine learning approach to predict associations between mammals and multiple coronaviruses and hence estimate the potential for generation of novel coronaviruses by recombination.
- Maya Wardeh
- , Matthew Baylis
- & Marcus S. C. Blagrove
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Article
| Open AccessIsolation of MERS-related coronavirus from lesser bamboo bats that uses DPP4 and infects human-DPP4-transgenic mice
Several human coronaviruses (CoV) have been proposed to emerge from bats but evidence of direct bat-to-human transmission is slim. In this work, the authors isolate a MERS-related CoV strain directly from bats and show that it infects target cells in vitro and engineered mice through the human DDP4 receptor.
- Susanna K. P. Lau
- , Rachel Y. Y. Fan
- & Patrick C. Y. Woo
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Article
| Open AccessOrigin of rebound virus in chronically SIV-infected Rhesus monkeys following treatment discontinuation
The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression likely is the source of viral rebound following ART discontinuation.
- Po-Ting Liu
- , Brandon F. Keele
- & Dan H. Barouch
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Article
| Open AccessGene editing and elimination of latent herpes simplex virus in vivo
Herpes simplex virus establishes lifelong latency in ganglionic neurons, which are the source for recurrent infection. Here Aubert et al. report a promising antiviral therapy based on gene editing with adeno-associated virus-delivered meganucleases, which leads to a significant reduction in ganglionic HSV loads and HSV reactivation.
- Martine Aubert
- , Daniel E. Strongin
- & Keith R. Jerome
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Article
| Open AccessSingle-cell TCR sequencing reveals phenotypically diverse clonally expanded cells harboring inducible HIV proviruses during ART
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
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Article
| Open AccessClearance of HIV infection by selective elimination of host cells capable of producing HIV
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
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Article
| Open AccessResident memory T cells are a cellular reservoir for HIV in the cervical mucosa
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
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Article
| Open AccessExpression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab
Here, the authors identify B lymphocyte antigen CD20 as a marker for HIV-infected T cells and provide evidence for the potential use of anti-CD20 antibodies in combination with latency reversing agents for depletion of viral reactivated CD4 T cells in patients on antiretroviral therapy.
- Carla Serra-Peinado
- , Judith Grau-Expósito
- & Maria J. Buzon
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Article
| Open AccessA majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation
HIV infected cells persist for decades in patients under ART, but the mechanisms responsible remain unclear. Here, Reeves et al. use modeling approaches adapted from ecology to show that cellular proliferation, rather than viral replication, generates a majority of infected cells during ART.
- Daniel B. Reeves
- , Elizabeth R. Duke
- & Joshua T. Schiffer
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Article
| Open AccessMale germ cells support long-term propagation of Zika virus
Zika virus (ZIKV) can persist for months in semen and sperm. Here, the authors show that germ cells, compared to other cell types in the reproductive tract, are most susceptible to ZIKV and produce high levels of progeny virus, which coincides with decreased expression of the interferon-stimulated gene Ifi44l.
- Christopher L. Robinson
- , Angie C. N. Chong
- & Shuibing Chen
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Article
| Open AccessHIV-1-mediated insertional activation of STAT5B and BACH2 trigger viral reservoir in T regulatory cells
HIV insertions in hematopoietic cells are enriched in BACH2 or MLK2 genes, but the selective advantages conferred are unknown. Here, the authors show that BACH2 and additionally STAT5B are activated by viral insertions, generating chimeric mRNAs specifically enriched in T regulatory cells favoring their persistence.
- Daniela Cesana
- , Francesca R. Santoni de Sio
- & Eugenio Montini
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Article
| Open AccessExtinct type of human parvovirus B19 persists in tonsillar B cells
The cell type that hosts parvovirus B19 (B19V) DNA lifelong is currently unknown. Here, the authors identify tonsillar B cells as a reservoir, detect an extinct B19V type in older adults, supporting a long-term association, and show that B19V uptake into B cells is antibody dependent.
- Lari Pyöriä
- , Mari Toppinen
- & Maria F. Perdomo
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Article
| Open AccessModelling filovirus maintenance in nature by experimental transmission of Marburg virus between Egyptian rousette bats
Bats are natural hosts for Marburg virus (MARV), but the mechanism of bat-to-bat transmission is unclear. Here, Schuhet al. monitor MARV infection in a cohort of 38 bats over nine months, find ‘supershedders’ and show that MARV can horizontally transmit between bats.
- Amy J. Schuh
- , Brian R. Amman
- & Jonathan S. Towner
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Article
| Open AccessBroad activation of latent HIV-1 in vivo
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.
- Kirston Barton
- , Bonnie Hiener
- & Sarah Palmer
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Article
| Open AccessElimination of HIV-1-infected cells by broadly neutralizing antibodies
Broadly neutralizing antibodies (bNAbs) are promising as potential therapies targeting HIV-1 but their overall antiviral activity remains to be fully elucidated. Here the authors evaluate the ability of a panel of bNAbs to trigger antibody-dependent cellular cytotoxicity and identify the most effective antibody combinations.
- Timothée Bruel
- , Florence Guivel-Benhassine
- & Olivier Schwartz
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Article
| Open AccessActivation and lysis of human CD4 cells latently infected with HIV-1
The elimination of latently infected cells is a sought after goal in the treatment of HIV-1 infections. Here the authors develop an approach to eliminate latently HIV-1 infected cells by using an immunomodulatory protein, which can activate viral gene expression in these cells and direct T lymphocytes to lyse them in vitro.
- Amarendra Pegu
- , Mangaiarkarasi Asokan
- & Gary J. Nabel
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Article
| Open AccessProgressive contraction of the latent HIV reservoir around a core of less-differentiated CD4+ memory T Cells
HIV can persist in CD4+T cells of patients receiving long-term antiretroviral therapy. Here the authors show the presence of intrinsic dynamics that progressively contract the latent HIV reservoir around a core of less-differentiated CD4 T-cell memory subsets.
- S. Jaafoura
- , M. G. de Goër de Herve
- & Y. Taoufik