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Sci Rep 2021 06 14;11(1):12448. Epub 2021 Jun 14.

Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.

The SARS-CoV-2 spike glycoprotein is a focal point for vaccine immunogen and therapeutic antibody design, and also serves as a critical antigen in the evaluation of immune responses to COVID-19. A common feature amongst enveloped viruses such as SARS-CoV-2 and HIV-1 is the propensity for displaying host-derived glycans on entry spike proteins. Similarly displayed glycosylation motifs can serve as the basis for glyco-epitope mediated cross-reactivity by antibodies, which can have important implications on virus neutralization, antibody-dependent enhancement (ADE) of infection, and the interpretation of antibody titers in serological assays. Read More

AIDS 2021 Jun 14. Epub 2021 Jun 14.

Department of Infectious Diseases, King's College London, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK Medical Research Council/Uganda Virus Research Institute, Entebbe, Uganda Projeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro RJ 21941-901, Brazil Department of Infectious Diseases, Ospedale San Raffaele, Milan 20132, Italy Department of Medicine, Imperial College London, UK Infectious Diseases Service. Hospital Clinic-Institut d'investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, United Kingdom MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology St Vincent's Centre for Applied Medical Research and The Kirby Institute, UNSW Australia, Sydney, New South Wales 2052, Australia Brighton and Sussex University Hospitals, Brighton, United Kingdom HIV Prevention Research Unit, South African Medical Research Council, Durban, South Africa Department of Infectious Disease, Imperial College London, London, UK; NIHR Imperial Biomedical Research Centre, London, UK Nuffield Department of Medicine, Oxford University, UK; Oxford NIHR Biomedical Research Centre, Oxford, UK King's College NIHR Research Biomedical Research Centre, London, UK Current Address, Imperial College London These Authors contributed equally to the work Deceased.

Objective: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 Envelope based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts. Read More

BMC Infect Dis 2021 Jun 14;21(1):569. Epub 2021 Jun 14.

Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan.

Background: NEW LAV BLOT I and II (LAV I and LAV II), they were only option for human immunodeficiency virus (HIV) confirmatory test, following HIV screening test using HIV Ag/Ab combination test in Japan. We evaluated the performance of Geenius HIV-1/2 Confirmatory Assay (Geenius), both as a confirmatory test and for differentiation between HIV-1 and HIV-2, in comparison with LAV I and LAV II.

Methods: Eighty-nine HIV-1-positive plasma specimens, one anti-HIV-1 low-titer performance panel, 10 seroconversion panels, and two anti-HIV-1/2 combo performance panels were tested. Read More

Nucleic Acids Res 2021 Jun 14. Epub 2021 Jun 14.

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.

Elucidating the structure of RNA and RNA ensembles is essential to understand biological functions. In this work, we explored the previously uncharted reactivity of bis-chloropiperidines (B-CePs) towards RNA. We characterized at the molecular level the different adducts induced by the fast reacting compound B-CeP 1 with RNA. Read More

PLoS Pathog 2021 Jun 14;17(6):e1009647. Epub 2021 Jun 14.

AIDS Institute, Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.

HIV-1 functional cure requires sustained viral suppression without antiretroviral therapy. While effector-memory CD8+ T lymphocytes are essential for viremia control, few vaccines elicit such cellular immunity that could be potently recalled upon viral infection. Here, we investigated a program death-1 (PD1)-based vaccine by fusion of simian immunodeficiency virus capsid antigen to soluble PD1. Read More

Front Public Health 2021 26;9:690017. Epub 2021 May 26.

Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, United States.

Despite substantial progress in confronting the global HIV-1 epidemic since its inception in the 1980s, better approaches for both treatment and prevention will be necessary to end the epidemic and remain a top public health priority. Antiretroviral therapy (ART) has been effective in extending lives, but at a cost of lifelong adherence to treatment. Broadly neutralizing antibodies (bNAbs) are directed to conserved regions of the HIV-1 envelope glycoprotein trimer (Env) and can block infection if present at the time of viral exposure. Read More

Chem Sci 2021 Apr 5;12(20):7174-7184. Epub 2021 Apr 5.

Physical Sciences for Health Centre, University of Birmingham Edgbaston Birmingham B15 2TT UK.

RNA targeting is an exciting frontier for drug design. Intriguing targets include functional RNA structures in structurally-conserved untranslated regions (UTRs) of many lethal viruses. However, computational docking screens, valuable in protein structure targeting, fail for inherently flexible RNA. Read More

Chem Sci 2020 Jul 6;11(30):7910-7920. Epub 2020 Jul 6.

Department of Chemistry, Indian Institute of Science Education and Research Bhopal Bhopal Bypass Road, Bhauri Bhopal 462066 Madhya Pradesh India

Porous organic frameworks (POFs) with a heteroatom rich ionic backbone have emerged as advanced materials for catalysis, molecular separation, and antimicrobial applications. The loading of metal ions further enhances Lewis acidity, augmenting the activity associated with such frameworks. Metal-loaded ionic POFs, however, often suffer from physicochemical instability, thereby limiting their scope for diverse applications. Read More

Front Immunol 2021 26;12:667393. Epub 2021 May 26.

Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, United States.

Humanized bone marrow-liver-thymus (HuBLT) mice are a revolutionary small-animal model that has facilitated the study of human immune function and human-restricted pathogens, including human immunodeficiency virus type 1 (HIV-1). These mice recapitulate many aspects of acute and chronic HIV-1 infection, but exhibit weak and variable T-cell responses when challenged with HIV-1, hindering our ability to confidently detect HIV-1-specific responses or vaccine effects. To identify the cause of this, we comprehensively analyzed T-cell development, diversity, and function in HuBLT mice. Read More

Front Microbiol 2021 28;12:670016. Epub 2021 May 28.

Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, United States.

A unique population of HIV-1 infected individuals can control infection without antiretroviral therapy. These individuals fall into a myriad of categories based on the degree of control (low or undetectable viral load), the durability of control over time and the underlying mechanism (i.e. Read More

Front Microbiol 2021 26;12:629153. Epub 2021 May 26.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Viral DNA integrated in host cells is a major barrier to completely curing HIV-1. However, genome editing using the recently developed technique of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 has the potential to eradicate HIV-1. The present study aimed to use a lentiviral vector-based CRISPR/Cas9 system combined with dual-small/single guide RNAs (sgRNAs) to attack HIV-1 DNA in the latency reactivation model J-Lat 10. Read More

Saudi J Biol Sci 2021 Jun 17;28(6):3607-3615. Epub 2021 Mar 17.

Unit of Biochemistry, Faculty of Medicine, AIMST University, Semeling, Bedong, Kedah, Malaysia.

Background: Exosomes are nano-sized membrane vesicles, secreted by different types of cells into the body's biological fluids. They are found in abundance in semen as compared to other fluids. Exosomes contain a cargo of lipid molecules, proteins, phospholipids, cholesterol, mRNAs, and miRNAs. Read More

Angew Chem Int Ed Engl 2021 Jun 13. Epub 2021 Jun 13.

Tottori University: Tottori Daigaku, Graduate School of Engineering, JAPAN.

Enzymes catalyzing [4+2] cycloaddition have attracted increasing attention because of their key roles in natural product biosynthesis. Here, we solved the X-ray crystal structures of a pair of decalin synthases, Fsa2 and Phm7, that catalyze intramolecular [4+2] cycloadditions to form enantiomeric decalin scaffolds during biosynthesis of the HIV-1 integrase inhibitor equisetin and its stereochemical opposite, phomasetin. Computational modeling, using molecular dynamics simulations as well as quantum chemical calculations, demonstrates that the reactions proceed through synergetic conformational constraints assuring transition state-like substrates folds and their stabilization by specific protein-substrate interactions. Read More

EMBO J 2021 Jun 14:e106540. Epub 2021 Jun 14.

Institut de Recherche en Infectiologie de Montpellier, University of Montpellier, CNRS, Montpellier, France.

Dendritic cells (DC) subsets, like Langerhans cells (LC), are immune cells involved in pathogen sensing. They express specific antimicrobial cellular factors that are able to restrict infection and limit further pathogen transmission. Here, we identify the alarmin S100A9 as a novel intracellular antiretroviral factor expressed in human monocyte-derived and skin-derived LC. Read More

J Int AIDS Soc 2021 Jun;24(6):e25747

Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Introduction: Vaginal rings are a promising approach to provide a woman-centred, long-acting HIV prevention strategy. Prior trials of a 25 mg dapivirine (DPV) ring have shown a favourable safety profile and approximately 30% risk reduction of HIV-1 infection. Extended duration rings replaced every three months may encourage user adherence, improve health service efficiency and reduce cost overall. Read More

AIDS Behav 2021 Jun 11. Epub 2021 Jun 11.

University of Washington, Seattle, USA.

Understanding characteristics associated with adherence to pre-exposure prophylaxis (PrEP) methods for HIV-1 prevention may assist with optimizing implementation efforts. The dapivirine vaginal ring is a novel topical PrEP delivery method. Using data from a randomized, double-blind, placebo-controlled, phase III trial of the dapivirine vaginal ring conducted in four African countries, generalized estimating equation models were used to evaluate correlates of ring adherence. Read More

Nat Rev Immunol 2021 Jun 11. Epub 2021 Jun 11.

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Natural killer (NK) cells play an important role in innate immune responses to viral infections. Here, we review recent insights into the role of NK cells in viral infections, with particular emphasis on human studies. We first discuss NK cells in the context of acute viral infections, with flavivirus and influenza virus infections as examples. Read More

J Clin Rheumatol 2021 Jun 9. Epub 2021 Jun 9.

From the Division of Rheumatology, The University of Texas-McGovern Medical School, Houston, TX Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

AIDS 2021 Jun 9. Epub 2021 Jun 9.

Orlando Immunology Center, Orlando, FL, USA Baylor University Medical Center, Dallas, TX, USA Desert AIDS Project, Palm Springs, CA, USA Bliss Healthcare Services, Orlando, FL, USA Infectious Disease Specialists of Atlanta, Decatur, GA, USA Midway Immunology and Research Center, Fort Pierce, FL, USA ViiV Healthcare, Research Triangle Park, NC, USA GlaxoSmithKline, Brentford, UK ViiV Healthcare, Brentford, UK Stanford University, Palo Alto, CA.

Objectives: Dolutegravir/lamivudine (DTG/3TC) is indicated for treatment-naive and experienced people with HIV; however, questions remain about its utility in a test-and-treat setting because of potential transmitted resistance and baseline hepatitis B virus (HBV) co-infection. We present feasibility and efficacy of DTG/3TC in newly diagnosed individuals in a test-and-treat setting.

Design: The single-arm STAT study evaluated DTG/3TC in a US test-and-treat setting. Read More

AIDS 2021 Jun 10. Epub 2021 Jun 10.

KEMRI Wellcome Trust Research Programme, Kilifi, Kenya Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg South Africa Africa Health Research Institute, Durban, South Africa HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa Max Planck Institute for Infection Biology, Berlin, Germany Division of Infection and Immunity, University College London, London, UK Antibody Immunity Research Unit, University of the Witwatersrand, Johannesburg, South Africa.

Objectives: Antibody function has been extensively studied in HIV infected adults but is relatively understudied in children. Emerging data suggests enhanced development of broadly neutralizing antibodies (bNAbs) in children, but Fc effector functions in this group are less well-defined. Here, we profiled overall antibody function in HIV infected children. Read More

Elife 2021 Jun 11;10. Epub 2021 Jun 11.

Institut de Recherche en Infectiologie de Montpellier (IRIM), CNRS Délégation Languedoc Roussillon - Montpellier University, Montpellier, France.

During HIV-1 particle formation, the requisite plasma membrane curvature is thought to be solely driven by the retroviral Gag protein. Here, we reveal that the cellular I-BAR protein IRSp53 is required for the progression of HIV-1 membrane curvature to complete particle assembly. SiRNA-mediated knockdown of IRSp53 gene expression induces a decrease in viral particle production and a viral bud arrest at half completion. Read More

Curr Res Struct Biol 2020 19;2:222-228. Epub 2020 Oct 19.

Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT, 06511, USA.

From cellular deposition of the HIV-1 capsid to integration of the viral genome, the capsid constitutes a primary target of a variety of host proteins that work to either promote or inhibit HIV-1 infection. Successful progression of HIV-1 infection depends on interactions between the capsid and host factors involved in stability, cellular transport, nuclear import, and genome integration. The virus must also guard its reverse-transcribing genome inside the capsid from host restriction factors that bind the capsid and suppress infection. Read More

HIV AIDS (Auckl) 2021 3;13:605-615. Epub 2021 Jun 3.

High Altitude Exercise Physiology, Western Colorado University, Gunnison, CO, USA.

Purpose: Cardiovascular disease (CVD) risk assessment is a suitable way to differentiate between high-risk individuals requiring intervention and risk modification, and those at low risk. However, concerns have been raised when adopting a CVD-risk prediction algorithm for HIV-infected patients in sub-Saharan Africa.

Patients And Methods: We compared cardiovascular risk profiles between HIV-infected (with and without antiretroviral therapy (ART)) and HIV-uninfected adults as predicted by the American College of Cardiology/American Heart Association (ASCVD) and the Framingham cardiovascular risk score (FRS) algorithms and assessed the concordance of the algorithms in predicting 10-year CVD risk separately in HIV-infected and uninfected groups in a hospital-based cross-sectional study in Tanzania. Read More

Biochem Biophys Res Commun 2021 Jun 7;566:30-35. Epub 2021 Jun 7.

Department of Biology, Georgia State University, Atlanta, GA, 30303, USA; Department of Chemistry, Georgia State University, Atlanta, GA, 30303, USA. Electronic address:

The emergence of multidrug resistant (MDR) HIV strains severely reduces the effectiveness of antiretroviral therapy. Clinical inhibitor darunavir (1) has picomolar binding affinity for HIV-1 protease (PR), however, drug resistant variants like PR show poor inhibition by 1, despite the presence of only two mutated residues in the inhibitor-binding site. Antiviral inhibitors that target MDR proteases like PR would be valuable as therapeutic agents. Read More

Cell Host Microbe 2021 06;29(6):849-851

Department for Microbiology and Clinical Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

One barrier to HIV-1 eradication is the viral Env protein that is invisible to most antibodies. In this issue of Cell Host & Microbe, Rajashekar et al. (2021) remove the "invisibility cloak" from Env, make it accessible to antibodies, and demonstrate NK-mediated in vivo killing of infected cells by human plasma antibodies. Read More

J Clin Pharm Ther 2021 Jun 10. Epub 2021 Jun 10.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.

What Is Known And Objective: Treatment for diffuse large B-cell lymphoma (DLBCL) in persons with AIDS consists of chemotherapy alongside antiretroviral therapy (ART). To determine optimal HIV treatment, drug-drug interactions, toxic effects and ART resistance must be considered.

Case Description: A 40-year-old man with drug-resistant HIV and DLBCL initiating chemotherapy which had drug interactions with his ART. Read More

J Acquir Immune Defic Syndr 2021 Jun 8. Epub 2021 Jun 8.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, MA, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, Makerere University - Johns Hopkins University Research Collaboration, Kampala, Uganda, Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, , University of Zimbabwe, Harare, Zimbabwe, University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe, Department of Pediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa, Division of AIDS, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD, Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD, FHI 360, Durham, NC, Department of Pediatrics, University of Washington, Seattle, WA, Seattle Children's Research Institute, Seattle, WA, University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi, Department of Obstetrics and Gynecology, College of Medicine, University of Malawi, Blantyre, Malawi, Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa, Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College and Johns Hopkins Clinical Trials Unit, Pune, India, Department of Pediatrics and Child Health, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa, Department of Pediatrics, Kilimanjaro Christian Medical Centre and Kilimanjaro Christian Medical University College, Moshi, Tanzania, Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, Perinatal HIV Research Unit, Chris Baragwanath Hospital, Johannesburg, South Africa, Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.

Background: Breastfeeding mothers with HIV infection not qualifying for antiretroviral therapy (ART) based on country-specific guidelines at the time of the PROMISE trial and their uninfected neonates were randomized to maternal ART (mART) or infant nevirapine prophylaxis (iNVP) postpartum. HIV transmission proportions were similar (< 1%) in the two arms. We assessed whether maternal viral load (MVL) or CD4 cell counts were associated with breastfeeding HIV transmission. Read More

AIDS Res Hum Retroviruses 2021 Jun 9. Epub 2021 Jun 9.

University of Venda, 56868, Microbiology, Thohoyandou, Limpopo, South Africa.

South Africa introduced the "diagnose and treat" HIV treatment programme in September 2016. The programme enables diagnosed HIV positive patients to start treatment. However, the presence of drug resistant (DR) viruses in the drug naïve population complicates the choice of ART. Read More

AIDS Res Hum Retroviruses 2021 Jun 9. Epub 2021 Jun 9.

Gansu Provincial Center for Disease Control and Prevention, Lanzhou, China;

Objectives: It is important to monitor the diversity and evolution of HIV-1 genotypes especially in some remote and undeveloped regions in China where the diversity and distribution of HIV-1 genotypes are not fully clear.

Methods: To investigate the genotypes and distribution of HIV-1 in far Northwestern Gansu Province of China, we selected 220 HIV-1 positive plasma samples from the center of disease prevention and control (CDC) in Gansu from January 2016 to December 2018. The viral load of inclusion samples were over 1000 copies per milliliter. Read More

Top Antivir Med 2021 Apr-May;29(2):334-343

University of California San Diego, San Diego, CA, USA.

The 2021 Conference on Retroviruses and Opportunistic Infections (CROI) featured a timely review of the neurologic complications of COVID-19 as well as new research findings on mechanisms by which SARS-CoV-2 may affect the brain. CROI included new and important findings about the neurologic complications of HIV-1, human polyomavirus 2 (also known as JC Virus), and cryptococcus. New long-term analyses of cognition in people with HIV-1 identified that cognitive decline over time is associated with multimorbidity, particularly diabetes, chronic lung disease, and vascular disease risk conditions. Read More