Articles

Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir

Integrase strand transfer inhibitors (INSTIs) are recommended for first-line HIV therapy based on their relatively high genetic barrier to resistance. Although raltegravir (RAL) and elvitegravir (EVG) resistan...

Authors: Maureen Oliveira, Ruxandra-Ilinca Ibanescu, Kaitlin Anstett, Thibault Mésplède, Jean-Pierre Routy, Marjorie A. Robbins and Bluma G. Brenner

The role of follicular helper CD4 T cells in the development of HIV-1 specific broadly neutralizing antibody responses

The induction of HIV-1-specific antibodies that can neutralize a broad number of isolates is a major goal of HIV-1 vaccination strategies. However, to date no candidate HIV-1 vaccine has successfully elicited ...

Authors: Eirini Moysi, Constantinos Petrovas and Richard A. Koup

HIV-1 cell-to-cell transmission and broadly neutralizing antibodies

HIV-1 spreads through contacts between infected and target cells. Polarized viral budding at the contact site forms the virological synapse. Additional cellular processes, such as nanotubes, filopodia, virus a...

Authors: Jérémy Dufloo, Timothée Bruel and Olivier Schwartz

Broadly neutralizing antibodies: What is needed to move from a rare event in HIV-1 infection to vaccine efficacy?

The elicitation of broadly neutralizing antibodies (bnAbs) is considered crucial for an effective, preventive HIV-1 vaccine. Led by the discovery of a new generation of potent bnAbs, the field has significantl...

Authors: Harini Subbaraman, Merle Schanz and Alexandra Trkola

Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design

A central puzzle in HIV-1 research is the inability of vaccination or even infection to reliably elicit humoral responses against broadly neutralizing epitopes in the HIV-1 envelope protein. In infected indivi...

Authors: Joel Finney and Garnett Kelsoe

Cell surface ectodomain integrity of a subset of functional HIV-1 envelopes is dependent on a conserved hydrophilic domain containing region in their C-terminal tail

HIV-1 Env gp160 is cleaved to form gp120 and gp41 and the functional HIV-1 Env is a trimer of non-covalently associated heterodimeric subunits, gp120 and gp41. The cleaved, native, trimeric form of Envs expose...

Authors: Sweety Samal, Supratik Das, Saikat Boliar, Huma Qureshi, Tripti Shrivastava, Naresh Kumar, Sandeep Goswami, Manish Bansal and Bimal K. Chakrabarti

Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity

Semen is a critical vector for human immunodeficiency virus (HIV) sexual transmission and harbors seminal amyloid fibrils that can markedly enhance HIV infection. Semen-derived enhancer of viral infection (SEV...

Authors: Ruxia Ren, Shuwen Yin, Baolong Lai, Lingzhen Ma, Jiayong Wen, Xuanxuan Zhang, Fangyuan Lai, Shuwen Liu and Lin Li

The invariant arginine within the chromatin-binding motif regulates both nucleolar localization and chromatin binding of Foamy virus Gag

Nuclear localization of Gag is a property shared by many retroviruses and retrotransposons. The importance of this stage for retroviral replication is still unknown, but studies on the Rous Sarcoma virus indic...

Authors: Joris Paris, Joëlle Tobaly-Tapiero, Marie-Lou Giron, Julien Burlaud-Gaillard, Florence Buseyne, Philippe Roingeard, Pascale Lesage, Alessia Zamborlini and Ali Saïb

Quantitation of the latent HIV-1 reservoir from the sequence diversity in viral outgrowth assays

The ability of HIV-1 to integrate into the genomes of quiescent host immune cells, establishing a long-lived latent viral reservoir (LVR), is the primary obstacle to curing these infections. Quantitative viral...

Authors: Art F. Y. Poon, Jessica L. Prodger, Briana A. Lynch, Jun Lai, Steven J. Reynolds, Jingo Kasule, Adam A. Capoferri, Susanna L. Lamers, Christopher W. Rodriguez, Daniel Bruno, Stephen F. Porcella, Craig Martens, Thomas C. Quinn and Andrew D. Redd

Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs

Co-infection with avian leukosis virus subgroup J and reticuloendotheliosis virus induces synergistic pathogenic effects and increases mortality. However, the role of exosomal miRNAs in the molecular mechanism...

Authors: Defang Zhou, Jingwen Xue, Shuhai He, Xusheng Du, Jing Zhou, Chengui Li, Libo Huang, Venugopal Nair, Yongxiu Yao and Ziqiang Cheng

CD8⁺ T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication

Development of AIDS vaccines for effective prevention of circulating HIV-1 is required, but no trial has demonstrated definitive effects on the prevention. Several recent T-cell vaccine trials showed no protec...

Authors: Hayato Murakoshi, Chengcheng Zou, Nozomi Kuse, Tomohiro Akahoshi, Takayuki Chikata, Hiroyuki Gatanaga, Shinichi Oka, Tomáš Hanke and Masafumi Takiguchi

Global phosphoproteomics of CCR5-tropic HIV-1 signaling reveals reprogramming of cellular protein production pathways and identifies p70-S6K1 and MK2 as HIV-responsive kinases required for optimal infection of CD4+ T cells

Viral reprogramming of host cells enhances replication and is initiated by viral interaction with the cell surface. Upon human immunodeficiency virus (HIV) binding to CD4+ T cells, a signal transduction cascad...

Authors: Danica D. Wiredja, Caroline O. Tabler, Daniela M. Schlatzer, Ming Li, Mark R. Chance and John C. Tilton

The KT Jeang Retrovirology prize 2018: Eric Freed

Authors:

The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a post-transcriptional level

The ability of human immunodeficiency virus type 1 (HIV-1) to form a stable viral reservoir is the major obstacle to an HIV-1 cure and post-transcriptional events contribute to the maintenance of viral latency...

Authors: Shringar Rao, Raquel Amorim, Meijuan Niu, Abdelkrim Temzi and Andrew J. Mouland

Super-resolution fluorescence microscopy studies of human immunodeficiency virus

Super-resolution fluorescence microscopy combines the ability to observe biological processes beyond the diffraction limit of conventional light microscopy with all advantages of the fluorescence readout such ...

Authors: Jakub Chojnacki and Christian Eggeling

Obituary: Remembering Professor David Cooper

Authors: Stuart Turville and Anthony Kelleher

HIV-1 Tat phosphorylation on Ser-16 residue modulates HIV-1 transcription

HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Here we analyzed Tat phosphorylation in cultured cells and its functi...

Authors: Andrey Ivanov, Xionghao Lin, Tatiana Ammosova, Andrey V. Ilatovskiy, Namita Kumari, Hatajai Lassiter, Nowah Afangbedji, Xiaomei Niu, Michael G. Petukhov and Sergei Nekhai

Efficacies of Cabotegravir and Bictegravir against drug-resistant HIV-1 integrase mutants

Integrase strand transfer inhibitors (INSTIs) are the class of antiretroviral (ARV) drugs most recently approved by the FDA for the treatment of HIV-1 infections. INSTIs block the strand transfer reaction cata...

Authors: Steven J. Smith, Xue Zhi Zhao, Terrence R. Burke Jr. and Stephen H. Hughes

Replacement of feline foamy virus bet by feline immunodeficiency virus vif yields replicative virus with novel vaccine candidate potential

Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This ...

Authors: Carmen Ledesma-Feliciano, Sarah Hagen, Ryan Troyer, Xin Zheng, Esther Musselman, Dragana Slavkovic Lukic, Ann-Mareen Franke, Daniel Maeda, Jörg Zielonka, Carsten Münk, Guochao Wei, Sue VandeWoude and Martin Löchelt

HIV latency reversing agents act through Tat post translational modifications

Different classes of latency reversing agents (LRAs) are being evaluated to measure their effects in reactivating HIV replication from latently infected cells. A limited number of studies have demonstrated add...

Authors: Georges Khoury, Talia M. Mota, Shuang Li, Carolin Tumpach, Michelle Y. Lee, Jonathan Jacobson, Leigh Harty, Jenny L. Anderson, Sharon R. Lewin and Damian F. J. Purcell

Reconstruction of a replication-competent ancestral murine endogenous retrovirus-L

About 10% of the mouse genome is composed of endogenous retroviruses (ERVs) that represent a molecular fossil record of past retroviral infections. One such retrovirus, murine ERV-L (MuERV-L) is an env-deficient ...

Authors: Daniel Blanco-Melo, Robert J. Gifford and Paul D. Bieniasz

CLIP-related methodologies and their application to retrovirology

Virtually every step of HIV-1 replication and numerous cellular antiviral defense mechanisms are regulated by the binding of a viral or cellular RNA-binding protein (RBP) to distinct sequence or structural ele...

Authors: Paul D. Bieniasz and Sebla B. Kutluay

The HTLV-1 oncoprotein Tax is modified by the ubiquitin related modifier 1 (Urm1)

Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy secondary to chronic human T-cell lymphotropic virus 1 infection, triggered by the virally encoded oncoprotein Tax. The transforming activity an...

Authors: Rita Hleihel, Behzad Khoshnood, Ingrid Dacklin, Hayssam Omran, Carine Mouawad, Zeina Dassouki, Marwan El-Sabban, Margret Shirinian, Caroline Grabbe and Ali Bazarbachi

HIV-1 protease with leucine zipper fused at N-terminus exhibits enhanced linker amino acid-dependent activity

HIV-1 protease (PR) activation is triggered by Gag-Pol dimerization. Premature PR activation results in reduced virion yields due to enhanced Gag cleavage. A p6* transframe peptide located directly upstream of...

Authors: Fu-Hsien Yu and Chin-Tien Wang

New World feline APOBEC3 potently controls inter-genus lentiviral transmission

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) gene family appears only in mammalian genomes. Some A3 proteins can be incorporated into progeny virions and inhibit lentivir...

Authors: Yoriyuki Konno, Shumpei Nagaoka, Izumi Kimura, Keisuke Yamamoto, Yumiko Kagawa, Ryuichi Kumata, Hirofumi Aso, Mahoko Takahashi Ueda, So Nakagawa, Tomoko Kobayashi, Yoshio Koyanagi and Kei Sato

Total HIV DNA: a global marker of HIV persistence

Among the different markers of HIV persistence in infected cells, total HIV DNA is to date the most widely used. It allows an overall quantification of all viral forms of HIV DNA in infected cells, each playin...

Authors: Christine Rouzioux and Véronique Avettand-Fenoël

Six-helix bundle completion in the distal C-terminal heptad repeat region of gp41 is required for efficient human immunodeficiency virus type 1 infection

The native pre-fusion structure of gp120/gp41 complex of human immunodeficiency virus type 1 was recently revealed. In the model, the helices of gp41 (α6, α7, α8, and α9) form a four-helix collar underneath trime...

Authors: Dehua Liu, Hongyun Wang, Mizuki Yamamoto, Jiping Song, Rui Zhang, Qingling Du, Yasushi Kawaguchi, Jun-ichiro Inoue and Zene Matsuda

Pre-exposure prophylaxis (PrEP) in an era of stalled HIV prevention: Can it change the game?

Pre-exposure prophylaxis (PrEP) for HIV prevention has evolved significantly over the years where clinical trials have now demonstrated the efficacy of oral PrEP, and the field is scaling-up implementation. Th...

Authors: Robyn Eakle, Francois Venter and Helen Rees

Why was PERV not transmitted during preclinical and clinical xenotransplantation trials and after inoculation of animals?

Porcine endogenous retroviruses (PERVs) are present in the genome of all pigs, they infect certain human cells and therefore pose a special risk for xenotransplantation using pig cells, tissues and organs. Xen...

Authors: Joachim Denner

A CRISPR screen for factors regulating SAMHD1 degradation identifies IFITMs as potent inhibitors of lentiviral particle delivery

The InterFeron Induced TransMembrane (IFITM) proteins are interferon stimulated genes that restrict many viruses, including HIV-1. SAMHD1 is another restriction factor blocking replication of HIV-1 and other v...

Authors: Ferdinand Roesch, Molly OhAinle and Michael Emerman

An RNA-binding compound that stabilizes the HIV-1 gRNA packaging signal structure and specifically blocks HIV-1 RNA encapsidation

NSC260594, a quinolinium derivative from the NCI diversity set II compound library, was previously identified in a target-based assay as an inhibitor of the interaction between the HIV-1 (ψ) stem-loop 3 (SL3) ...

Authors: Carin K. Ingemarsdotter, Jingwei Zeng, Ziqi Long, Andrew M.L. Lever and Julia C. Kenyon

Predominant envelope variable loop 2-specific and gp120-specific antibody-dependent cellular cytotoxicity antibody responses in acutely SIV-infected African green monkeys

The initial envelope (Env)-specific antibody response in acutely HIV-1-infected individuals and simian immunodeficiency virus (SIV)-infected rhesus monkeys (RMs) is dominated by non-neutralizing antibodies tar...

Authors: Quang N. Nguyen, David R. Martinez, Jonathon E. Himes, R. Whitney Edwards, Qifeng Han, Amit Kumar, Riley Mangan, Nathan I. Nicely, Guanhua Xie, Nathan Vandergrift, Xiaoying Shen, Justin Pollara and Sallie R. Permar

Recent advances in retroviruses via cryo-electron microscopy

Cryo-electron microscopy has undergone a revolution in recent years and it has contributed significantly to a number of different areas in biological research. In this manuscript, we will describe some of the ...

Authors: Johnson Mak and Alex de Marco

Measuring integrated HIV DNA ex vivo and in vitro provides insights about how reservoirs are formed and maintained

The identification of the most appropriate marker to measure reservoir size has been a great challenge for the HIV field. Quantitative viral outgrowth assay (QVOA), the reference standard to quantify the amoun...

Authors: Marilia Rita Pinzone and Una O’Doherty

Measuring replication competent HIV-1: advances and challenges in defining the latent reservoir

Antiretroviral therapy cannot cure HIV-1 infection due to the persistence of a small number of latently infected cells harboring replication-competent proviruses. Measuring persistent HIV-1 is challenging, as ...

Authors: Zheng Wang, Francesco R. Simonetti, Robert F. Siliciano and Gregory M. Laird

Non-coding RNAs and retroviruses

Retroviruses can cause severe diseases such as cancer and acquired immunodeficiency syndrome. A unique feature in the life cycle of retroviruses is that their RNA genome is reverse transcribed into double-stra...

Authors: Xu Zhang, Xiancai Ma, Shuliang Jing, Hui Zhang and Yijun Zhang

Assessment of the gorilla gut virome in association with natural simian immunodeficiency virus infection

Simian immunodeficiency viruses (SIVs) of chimpanzees and gorillas from Central Africa crossed the species barrier at least four times giving rise to human immunodeficiency virus type 1 (HIV-1) groups M, N, O ...

Authors: Mirela D’arc, Carolina Furtado, Juliana D. Siqueira, Héctor N. Seuánez, Ahidjo Ayouba, Martine Peeters and Marcelo A. Soares

Beyond the replication-competent HIV reservoir: transcription and translation-competent reservoirs

Recent years have seen a substantial increase in the number of tools available to monitor and study HIV reservoirs. Here, we discuss recent technological advances that enable an understanding of reservoir dyna...

Authors: Amy E. Baxter, Una O’Doherty and Daniel E. Kaufmann

Aged Chinese-origin rhesus macaques infected with SIV develop marked viremia in absence of clinical disease, inflammation or cognitive impairment

Damage to the central nervous system during HIV infection can lead to variable neurobehavioral dysfunction termed HIV-associated neurocognitive disorders (HAND). There is no clear consensus regarding the neuro...

Authors: Stephanie J. Bissel, Kate Gurnsey, Hank P. Jedema, Nicholas F. Smith, Guoji Wang, Charles W. Bradberry and Clayton A. Wiley

Episomal HIV-1 DNA and its relationship to other markers of HIV-1 persistence

Reverse transcription of HIV-1 results in the generation of a linear cDNA that serves as the precursor to the integrated provirus. Other classes of extrachromosomal viral cDNA molecules can be found in acutely...

Authors: Javier Martinez-Picado, Ryan Zurakowski, María José Buzón and Mario Stevenson

HIV evolution and diversity in ART-treated patients

Characterizing HIV genetic diversity and evolution during antiretroviral therapy (ART) provides insights into the mechanisms that maintain the viral reservoir during ART. This review describes common methods u...

Authors: Gert van Zyl, Michael J. Bale and Mary F. Kearney

Digital PCR as a tool to measure HIV persistence

Although antiretroviral therapy is able to suppress HIV replication in infected patients, the virus persists and rebounds when treatment is stopped. In order to find a cure that can eradicate the latent reserv...

Authors: Sofie Rutsaert, Kobus Bosman, Wim Trypsteen, Monique Nijhuis and Linos Vandekerckhove

What do we measure when we measure cell-associated HIV RNA

Cell-associated (CA) HIV RNA has received much attention in recent years as a surrogate measure of the efficiency of HIV latency reversion and because it may provide an estimate of the viral reservoir size. Th...

Authors: Alexander O. Pasternak and Ben Berkhout

Prediction of HIV-associated neurocognitive disorder (HAND) from three genetic features of envelope gp120 glycoprotein

HIV-associated neurocognitive disorder (HAND) remains an important and yet potentially underdiagnosed manifestation despite the fact that the modern combination antiretroviral therapy (cART) has achieved effec...

Authors: Masato Ogishi and Hiroshi Yotsuyanagi

New windows into retroviral RNA structures

The multiple roles of both viral and cellular RNAs have become increasingly apparent in recent years, and techniques to model them have become significantly more powerful, enabling faster and more accurate vis...

Authors: Dhivya Jayaraman and Julia Claire Kenyon

Ribosome profiling of the retrovirus murine leukemia virus

The retrovirus murine leukemia virus (MuLV) has an 8.3 kb RNA genome with a simple 5′-gag-pol-env-3′ architecture. Translation of the pol gene is dependent upon readthrough of the gag UAG stop codon; whereas the

Authors: Nerea Irigoyen, Adam M. Dinan, Ian Brierley and Andrew E. Firth

Inducible HIV RNA transcription assays to measure HIV persistence: pros and cons of a compromise

With the increasing number of therapeutic strategies tested in humans to reduce the size of the latent reservoir, the development of a robust, precise and clinical trial scalable assay that measures the freque...

Authors: Johann Plantin, Marta Massanella and Nicolas Chomont

Rapid HIV disease progression following superinfection in an HLA-B*27:05/B*57:01-positive transmission recipient

The factors determining differential HIV disease outcome among individuals expressing protective HLA alleles such as HLA-B*27:05 and HLA-B*57:01 remain unknown. We here analyse two HIV-infected subjects expre...

Authors: Jacqui Brener, Astrid Gall, Jacob Hurst, Rebecca Batorsky, Nora Lavandier, Fabian Chen, Anne Edwards, Chrissy Bolton, Reena Dsouza, Todd Allen, Oliver G. Pybus, Paul Kellam, Philippa C. Matthews and Philip J. R. Goulder

Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA damage response

Viral protein R (Vpr) is an accessory protein of HIV-1, which is potentially involved in the infection of macrophages and the induction of the ataxia-telangiectasia and Rad3-related protein (ATR)-mediated DNA ...

Authors: Kenta Iijima, Junya Kobayashi and Yukihito Ishizaka

The HIV-1 accessory proteins Nef and Vpu downregulate total and cell surface CD28 in CD4⁺ T cells

The HIV-1 accessory proteins Nef and Vpu alter cell surface levels of multiple host proteins to modify the immune response and increase viral persistence. Nef and Vpu can downregulate cell surface levels of th...

Authors: Emily N. Pawlak, Brennan S. Dirk, Rajesh Abraham Jacob, Aaron L. Johnson and Jimmy D. Dikeakos