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Sign Up#21
Chris M Garza, Matthew Holcomb, Diogo Santos-Martins, Bruce E Torbett, Stefano Forli
The HIV-1 capsid is an irregularly shaped complex of about 1200 protein chains containing the viral genome and several viral proteins. Together, these components are the key to unlocking passage into the nucleus, allowing for permanent integration of the viral genome into the host cell genome. Recent interest into the role of the capsid in viral replication has been driven by the approval of the first-in-class drug lenacapavir, which marks the first drug approved to target a non-enzymatic HIV-1 viral protein...
March 12, 2024: bioRxiv
#22
Steven Weaver, Vanessa Dávila-Conn, Daniel Ji, Hannah Verdonk, Santiago Ávila-Ríos, Andrew J Leigh Brown, Joel O Wertheim, Sergei L Kosakovsky Pond
Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern...
March 14, 2024: bioRxiv
#23
Haley Durden, Benjamin Preece, Rodrigo Gallegos, Ipsita Saha, Brian MacArthur, Abby Petersen, Wiley Peppel, Saveez Saffarian
UNLABELLED: During assembly on the plasma membrane, HIV-1 virions incorporate Gag-Pol as well as gp120/gp41 trimers. The Pol region consists of protease, reverse transcriptase and integrase precursors which are essential enzymes required for maturation, reverse transcription, and integration of the viral genome in the next host. gp120/gp41 trimers catalyze the fusion of the virion with its next host. Only a fraction of released virions are infectious. The stoichiometry of gp120/gp41 and Gag-Pol proteins in HIV virions was previously measured using cryotomography and ratiometric protein analysis, but what is the stoichiometry of these proteins in infectious virions remained to be determined...
March 12, 2024: bioRxiv
#24
Dylan G Maghini, Ovokeraye H Oduaran, Jakob Wirbel, Luicer A Ingasia Olubayo, Natalie Smyth, Theophilous Mathema, Carl W Belger, Godfred Agongo, Palwendé R Boua, Solomon Sr Choma, F Xavier Gómez-Olivé, Isaac Kisiangani, Given R Mashaba, Lisa Micklesfield, Shukri F Mohamed, Engelbert A Nonterah, Shane Norris, Hermann Sorgho, Stephen Tollman, Floidy Wafawanaka, Furahini Tluway, Michèle Ramsay, Ami S Bhatt, Scott Hazelhurst
Population studies are crucial in understanding the complex interplay between the gut microbiome and geographical, lifestyle, genetic, and environmental factors. However, populations from low- and middle-income countries, which represent ∼84% of the world population, have been excluded from large-scale gut microbiome research. Here, we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,803 women from Burkina Faso, Ghana, Kenya, and South Africa. By intensively engaging with communities that range from rural and horticultural to urban informal settlements and post-industrial, we capture population diversity that represents a far greater breadth of the world's population...
March 14, 2024: bioRxiv
#25
JOURNAL ARTICLE
Jenna E Eschbach, Maritza Puray-Chavez, Shawn Mohammed, Qiankun Wang, Ming Xia, Lin-Chen Huang, Liang Shan, Sebla B Kutluay
UNLABELLED: A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1...
March 26, 2024: MBio
#26
JOURNAL ARTICLE
Hung Van Nguyen, Hoa Binh Nguyen, Doan Thu Ha, Dinh Thi Huong, Vu Ngoc Trung, Khieu Thi Thuy Ngoc, Tran Huyen Trang, Ha Vu Thi Ngoc, Tram Trinh Thi Bich, Trieu Le Pham Tien, Hanh Nguyen Hong, Phu Phan Trieu, Luong Kim Lan, Kim Lan, Ngo Ngoc Hue, Nguyen Thi Le Huong, Tran Le Thi Ngoc Thao, Nguyen Le Quang, Thu Do Dang Anh, Nguyễn Hữu Lân, Truong Van Vinh, Dang Thi Minh Ha, Phan Thuong Dat, Nguyen Phuc Hai, Derrick W Crook, Nguyen Thuy Thuong Thuong, Nhung Viet Nguyen, Guy E Thwaites, Timothy M Walker
OBJECTIVE: We conducted a descriptive analysis of multi-drug resistant tuberculosis (MDR-TB) in Vietnam's two largest cities, Hanoi and Ho Chi Minh city. METHODS: All patients with rifampicin resistant tuberculosis were recruited from Hanoi and surrounding provinces between 2020 and 2022. Additional patients were recruited from Ho Chi Minh city over the same time period. Demographic data were recorded from all patients, and samples collected, cultured, whole genome sequenced and analysed for drug resistance mutations...
May 2024: Journal of Clinical Tuberculosis and Other Mycobacterial Diseases
#27
JOURNAL ARTICLE
Chunlin Lan, Bo Zhu, Zhuo Hailong, Shi Yuting, Zixuan Sun, Zhang Lixuan, Lei Jia, Hanping Li, Jingyun Li, Yongjian Liu, Xiaolin Wang, Bohan Zhang, Jingwan Han, Junjun Jiang, Lin Li
With the prevalence of HIV-1 CRF01_AE and CRF07_BC subtypes in China, the co-circulation of multiple subtypes in HIV-1 positive population may result in dual infection or super-infection in the population, leading to the emergence of unique recombinant forms (URFs) of the HIV-1 virus. In this study, two second-generation unique recombinant strains, BI0114 and BI0116, were identified, and their near full-length genome sequences were obtained; recombination analysis showed that both sequences were the isoform of URF_0107, and they were second-generation unique recombinant strains formed by the recombination of CRF01_AE and CRF07_BC, and the isoforms were CRF01_AE and CRF0107_BC, respectively...
March 22, 2024: AIDS Research and Human Retroviruses
#28
JOURNAL ARTICLE
Ricardo Abrantes, Victor Pimentel, Mafalda N S Miranda, Ana Rita Silva, António Diniz, Bianca Ascenção, Carmela Piñeiro, Carmo Koch, Catarina Rodrigues, Cátia Caldas, Célia Morais, Domitília Faria, Elisabete Gomes da Silva, Eugénio Teófilo, Fátima Monteiro, Fausto Roxo, Fernando Maltez, Fernando Rodrigues, Guilhermina Gaião, Helena Ramos, Inês Costa, Isabel Germano, Joana Simões, Joaquim Oliveira, José Ferreira, José Poças, José Saraiva da Cunha, Jorge Soares, Sandra Fernandes, Kamal Mansinho, Liliana Pedro, Maria João Aleixo, Maria João Gonçalves, Maria José Manata, Margarida Mouro, Margarida Serrado, Micaela Caixeiro, Nuno Marques, Olga Costa, Patrícia Pacheco, Paula Proença, Paulo Rodrigues, Raquel Pinho, Raquel Tavares, Ricardo Correia de Abreu, Rita Côrte-Real, Rosário Serrão, Rui Sarmento E Castro, Sofia Nunes, Telo Faria, Teresa Baptista, Daniel Simões, Luis Mendão, M Rosário O Martins, Perpétua Gomes, Marta Pingarilho, Ana B Abecasis
INTRODUCTION: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. METHODS: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs)...
2024: Frontiers in Public Health
#29
Antigenic determinants of HAstV-VA1 neutralization and their relevance in the human immune response.
Inci Ramírez-Bello, Tomás López, Rafaela Espinosa, Anisa Ghosh, Kassidy Green, Lidia Riaño-Umbarila, Carlos Gaspar-Castillo, Celia M Alpuche-Aranda, Susana López, Rebecca M DuBois, Carlos F Arias
UNLABELLED: Astroviruses are highly divergent and infect a wide variety of animal hosts. In 2009, a genetically divergent human astrovirus (HAstV) strain VA1 was first identified in an outbreak of acute gastroenteritis. This strain has also been associated with fatal central nervous system disease. In this work, we report the isolation of three high-affinity neutralizing monoclonal antibodies (Nt-MAbs) targeting the capsid spike domain of HAstV-VA1. These antibodies (7C8, 2A2, 3D8) were used to select individual HAstV-VA1 mutants resistant to their neutralizing activity and also select a HAstV-VA1 triple mutant that escapes neutralization from all three Nt-MAbs...
March 5, 2024: bioRxiv
#30
JOURNAL ARTICLE
Yuxin Feng, Jianhua Lu, Lijing Wang, Yuling Wang, Jingyun Li, Hanping Li, Lin Li, Erhei Dai
The number of individuals infected with HIV-1 among men who have sex with men (MSM) has risen rapidly in recent years in China, and the subtypes CRF01_AE, CRF07_BC, and B, as well as many novel unique recombinant forms (URFs) are prevalent among them. Co-circulation of strains among MSM populations allows the generation of circulating recombinant forms (CRFs) and URFs. In this study, we identified two new URFs from two HIV-1-positive subjects who were infected through homosexual contact in Hebei, China. Analysis of near-full-length genome sequences, using phylogenetic and recombination analysis showed that the two URFs originated from CRF01_AE, CRF07_BC, and B, and CRF01_AE segments in the backbone of the URFs were derived from cluster 4 of CRF01_AE...
March 18, 2024: Archives of Virology
#31
JOURNAL ARTICLE
Jingyuan Luo, Qianyue Zhang, Shutong Wang, Luojie Zheng, Jie Liu, Yuchen Zhang, Yingchen Wang, Ranran Wang, Zhigang Xiao, Zheng Li
INTRODUCTION: UMP-CMP kinase 2 (CMPK2) is involved in mitochondrial DNA synthesis which can be oxidized and released into the cytoplasm in innate immunity. It initiates the assembly of NLRP3 inflammasomes and mediates various pathological processes such as human immunodeficiency virus infection and systemic lupus erythematosus. However the role of CMPK2 in tumor progression and tumor immunity remains unclear. METHOD: In this study we conducted a systematical analysis of CMPK2 across 33 different cancers based on datasets such as Genotype Tissue-Expression (GTEx) The Cancer Genome Atlas (TCGA) the Cancer Cell Line Encyclopedia (CCLE) and Tumor Immune Syngeneic Mouse (TISMO)...
March 13, 2024: Current Cancer Drug Targets
#32
JOURNAL ARTICLE
Roux-Cil Ferreira, Steven J Reynolds, Adam A Capoferri, Owen R Baker, Erin E Brown, Ethan Klock, Jernelle Miller, Jun Lai, Sharada Saraf, Charles Kirby, Briana Lynch, Jada Hackman, Sarah N Gowanlock, Stephen Tomusange, Samiri Jamiru, Aggrey Anok, Taddeo Kityamuweesi, Paul Buule, Daniel Bruno, Craig Martens, Rebecca Rose, Susanna L Lamers, Ronald M Galiwango, Art F Y Poon, Thomas C Quinn, Jessica L Prodger, Andrew D Redd
BACKGROUND: The principal barrier to an HIV cure is the presence of the latent viral reservoir (LVR), which has been understudied in African populations. From 2018 to 2019, Uganda instituted a nationwide rollout of ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen of one NNRTI and the same two NRTI. METHODS: Changes in the inducible replication-competent LVR (RC-LVR) of ART-suppressed Ugandans with HIV (n = 88) from 2015 to 2020 were examined using the quantitative viral outgrowth assay...
March 4, 2024: EBioMedicine
#33
JOURNAL ARTICLE
Charles Komen Chelimo, Paul Oyieng Angienda, Charles Ochieng Olwal, Henry Nyamogoba
BACKGROUND: Tuberculosis (TB) remains a high-burden infectious disease worldwide. Mycobacterium tuberculosis complex (MTBC) is the aetiological agent of TB. RESEARCH GAP: The TB burden is significantly linked to the development of drug-resistant strains. Thus, there is an urgent need for close surveillance of MTBC circulating in a given region, such as Western Kenya, for treatment of TB. AIM: To determine the proportion of MTBC species, strains and genetic diversities in circulation in HIV/AIDS-prevalent regions, and Western Kenya in particular...
2024: Access microbiology
#34
REVIEW
Kouki Matsuda, Kenji Maeda
Combination antiretroviral therapy (cART) has significantly improved the prognosis of individuals living with human immunodeficiency virus (HIV). Acquired immunodeficiency syndrome has transformed from a fatal disease to a treatable chronic infection. Currently, effective and safe anti-HIV drugs are available. Although cART can reduce viral production in the body of the patient to below the detection limit, it cannot eliminate the HIV provirus integrated into the host cell genome; hence, the virus will be produced again after cART discontinuation...
February 23, 2024: International Journal of Molecular Sciences
#35
JOURNAL ARTICLE
N A Kruglova, D S Komkov, D V Mazurov, M V Shepelev
Delivery of ribonucleoprotein complexes of Cas9 nuclease and guide RNA into target cells with virus-like particles (VLP) is one of the novel methods of genome editing and is suitable for gene therapy of human diseases in the future. The efficiency of genome editing with VLPs depends on the Cas9 packaging into VLPs, the process mediated by the viral Gag protein. To improve the packaging of Cas9 into NanoMEDIC VLPs, plasmid constructs for Cas9 and Gag expression were modified by adding the HIV Rev response element (RRE), which was expected to increase the nuclear export of RRE-containing transcripts into the cytosol via the Rev accessory protein, as described for a Vpr-Cas9-based VLP system...
March 12, 2024: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
#36
JOURNAL ARTICLE
Niklas Beschorner, Paul Künzle, Maike Voges, Ilona Hauber, Daniela Indenbirken, Jacqueline Nakel, Sanamjeet Virdi, Peter Bradtke, Niels Christian Lory, Michael Rothe, Maciej Paszkowski-Rogacz, Frank Buchholz, Adam Grundhoff, Axel Schambach, Christian Thirion, Hans-Willi Mittrücker, Julian Schulze Zur Wiesch, Joachim Hauber, Jan Chemnitz
Drug-based antiretroviral therapies (ART) efficiently suppress HIV replication in humans, but the virus persists as integrated proviral reservoirs in small numbers of cells. Importantly, ART cannot eliminate HIV from an infected individual, since it does not target the integrated provirus. Therefore, genome editing-based strategies that can inactivate or excise HIV genomes would provide the technology for novel curative therapies. In fact, the HIV-1 LTR-specific designer-recombinase Brec1 has been shown to remove integrated proviruses from infected cells and is highly efficacious on clinical HIV-1 isolates in vitro and in vivo, suggesting that Brec1 has the potential for clinical development of advanced HIV-1 eradication strategies in people living with HIV...
2024: PloS One
#37
JOURNAL ARTICLE
Benjamin Bone, Mathias Lichterfeld
PURPOSE OF REVIEW: Elite controllers (ECs) and Posttreatment controllers (PTCs) represent a small subset of individuals who are capable of maintaining drug-free control of HIV plasma viral loads despite the persistence of a replication-competent viral reservoir. This review aims to curate recent experimental studies evaluating viral reservoirs that distinguish EC/PTC and may contribute to their ability to maintain undetectable viral loads in the absence of antiretroviral therapy. RECENT FINDINGS: Recent studies on ECs have demonstrated that integration sites of intact proviruses in EC/PTC are markedly biased towards heterochromatin regions; in contrast, intact proviruses in accessible and permissive chromatin were profoundly underrepresented...
February 29, 2024: Current Opinion in HIV and AIDS
#38
JOURNAL ARTICLE
Weiling Li, Raunaq Malhotra, Steven Wu, Manjari Jha, Allen Rodrigo, Mary Poss, Raj Acharya
We present ViPRA-Haplo, a de novo strain-specific assembly workflow for reconstructing viral haplotypes in a viral population from paired-end next generation sequencing (NGS) data. The proposed Viral Path Reconstruction Algorithm (ViPRA) generates a subset of paths from a De Bruijn graph of reads using the pairing information of reads. The paths generated by ViPRA are an over-estimation of the true contigs. We propose two refinement methods to obtain an optimal set of contigs representing viral haplotypes. The first method clusters paths reconstructed by ViPRA using VSEARCH [1] based on sequence similarity, while the second method, MLEHaplo, generates a maximum likelihood estimate of viral populations...
March 7, 2024: IEEE/ACM Transactions on Computational Biology and Bioinformatics
#39
JOURNAL ARTICLE
Marie Morel, Anna Zhukova, Frédéric Lemoine, Olivier Gascuel
Evolutionary convergences are observed at all levels, from phenotype to DNA and protein sequences, and changes at these different levels tend to be correlated. Notably, convergent mutations can lead to convergent changes in phenotype, such as changes in metabolism, drug resistance, and other adaptations to changing environments. We propose a two-component approach to detect mutations subject to convergent evolution in protein alignments. The "Emergence" component selects mutations that emerge more often than expected, while the "Correlation" component selects mutations that correlate with the convergent phenotype under study...
March 7, 2024: Genome Biology and Evolution
#40
JOURNAL ARTICLE
HariOm Singh, Kishore Dhotre, Shyamveer, Ranjana Choudhari, Amita Verma, Supriya D Mahajan, Nemat Ali
BACKGROUND: The ABCG2 421C/A polymorphism contributes significantly to the distribution and absorption of antiretroviral (ARV) regimens and is associated with the undesirable side effects of efavirenz. METHODS: To investigate this, we examined ABCG2 34G/A (rs2231137) and 421C/A (rs2231142) genetic variations in 149 HIV-infected patients (116 without hepatotoxicity, 33 with ARV-induced hepatotoxicity) and 151 healthy controls through the PCR-restriction fragment length polymorphism (PCR-RFLP) technique...
March 7, 2024: Molecular Genetics & Genomic Medicine
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