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HIV bioinformatics

Michael Huber, Karin J Metzner, Fabienne D Geissberger, Cyril Shah, Christine Leemann, Thomas Klimkait, Jürg Böni, Alexandra Trkola, Osvaldo Zagordi
Genotypic monitoring of drug-resistance mutations (DRMs) in HIV-1 infected individuals is strongly recommended to guide selection of the initial antiretroviral therapy (ART) and changes of drug regimens. Traditionally, mutations conferring drug resistance are detected by population sequencing of the reverse transcribed viral RNA encoding the HIV-1 enzymes target by ART, followed by manual analysis and interpretation of Sanger sequencing traces. This process is labor intensive, relies on subjective interpretation from the operator, and offers limited sensitivity as only mutations above 20% frequency can be reliably detected...
November 17, 2016: Journal of Virological Methods
Maria Casadellà, Roger Paredes
The emerging HIV-1 resistance epidemic is threatening the impressive global advances in HIV-1 infection treatment and prevention achieved in the last decade. Next-generation sequencing is improving our ability to understand, diagnose and prevent HIV-1 resistance, being increasingly cost-effective and more accessible. However, NGS still faces a number of limitations that need to be addressed to enable its widespread use. Here, we will review the main NGS platforms available for HIV-1 diagnosis, the factors affecting the clinical utility of NGS testing and the evidence supporting -or not- ultrasensitive genotyping over Sanger sequencing for routine HIV-1 diagnosis...
November 3, 2016: Virus Research
Peter B Gilbert, Ying Huang, Holly E Janes
PURPOSE OF REVIEW: Models of implementation of known-effective interventions for HIV prevention indicate that an efficacious vaccine to prevent HIV infection would be critical for controlling the HIV pandemic. Key issues in the design of future HIV vaccine trials are: first, how to develop reliable immunological correlates of vaccine efficacy, second, how to down-select candidate vaccine regimens into efficacy trials, and third, how to learn about vaccine efficacy in the context of the evolving HIV prevention landscape...
November 2016: Current Opinion in HIV and AIDS
Carlo Mengoli, Samantha Andreis, Renzo Scaggiante, Mario Cruciani, Oliviero Bosco, Roberto Ferretto, Davide Leoni, Gaetano Maffongelli, Monica Basso, Carlo Torti, Loredana Sarmati, Massimo Andreoni, Giorgio Palù, Saverio Giuseppe Parisi
OBJECTIVES: To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log10 copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach. PATIENTS AND METHODS: Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0)...
September 7, 2016: Journal of Antimicrobial Chemotherapy
Hesam Montazeri, Jack Kuipers, Roger Kouyos, Jürg Böni, Sabine Yerly, Thomas Klimkait, Vincent Aubert, Huldrych F Günthard, Niko Beerenwinkel
UNLABELLED: The continuous time conjunctive Bayesian network (CT-CBN) is a graphical model for analyzing the waiting time process of the accumulation of genetic changes (mutations). CT-CBN models have been successfully used in several biological applications such as HIV drug resistance development and genetic progression of cancer. However, current approaches for parameter estimation and network structure learning of CBNs can only deal with a small number of mutations (<20). Here, we address this limitation by presenting an efficient and accurate approximate inference algorithm using a Monte Carlo expectation-maximization algorithm based on importance sampling...
September 1, 2016: Bioinformatics
Olga S Voitenko, Andi Dhroso, Anna Feldmann, Dmitry Korkin, Olga V Kalinina
MOTIVATION: Due to their high genomic variability, RNA viruses and retroviruses present a unique opportunity for detailed study of molecular evolution. Lentiviruses, with HIV being a notable example, are one of the best studied viral groups: hundreds of thousands of sequences are available together with experimentally resolved three-dimensional structures for most viral proteins. In this work, we use these data to study specific patterns of evolution of the viral proteins, and their relationship to protein interactions and immunogenicity...
September 1, 2016: Bioinformatics
Muhammad Sheraz, Mazhar Kanak, Mahmudul Hasan, Roshan Bhattarai, Kuhanandha Mahalingam, Leanna A Sealey, Rashshana R Blackwood, Zhabiz Golkar, Ewen McLean, Omar Bagasra
INTRODUCTION: Coinfection with certain members of the Flaviviridae, such as Dengue Virus (DV), West Nile Virus (WNV) Yellow Fever Virus (YFV) and most importantly, GBV-C have been documented to reduce HIV-1 viral load in vivo. Numerous studies strongly support the notion that persistent coinfection with non-pathogenic virus prolongs survival in HIV-1 infected individuals. Coinfected individuals show higher CD4+ cell counts, lower HIV-1 RNA viral loads and live three times longer than clinically matched HIV-1 monoinfected patients...
2016: Journal of Infection in Developing Countries
M N Zheng, T L Ning, Y J Gao, X Zhao, L Li, S H Cheng
OBJECTIVE: To understand the characteristics on the diversity of HIV subtypes and related transmission in Tianjin. METHODS: A total of 77 newly diagnosed ART-naïve HIV infectors in 2015 were screened by CD4(+) T cell counts ≥200 cells/μl. Viral RNAs were extracted from plasma samples. Reverse transcription PCR and nested PCR were used to analyze the amplification of pol and env gene fragments, sequencing, and related bioinformatics information. RESULTS: 46...
August 10, 2016: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
Marcus Buggert, Juliet Frederiksen, Ole Lund, Michael R Betts, Antonio Biague, Morten Nielsen, Johanna Tauriainen, Hans Norrgren, Patrik Medstrand, Annika C Karlsson, Marianne Jansson
OBJECTIVE: HIV type 2 (HIV-2) represents an attenuated form of HIV, in which many infected individuals remain 'aviremic' without antiretroviral therapy. However, aviremic HIV-2 disease progression exists, and in the current study, we therefore aimed to examine if specific pathological characteristics of CD4 T cells are linked to such outcome. DESIGN: HIV-seronegative (n = 25), HIV type 1 (HIV-1) (n = 33), HIV-2 (n = 39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n = 13)-infected study participants were enrolled from an occupational cohort in Guinea-Bissau...
October 23, 2016: AIDS
Mamneet Manghera, Jennifer Ferguson-Parry, Rongtuan Lin, Renée N Douville
UNLABELLED: Thousands of endogenous retroviruses (ERV), viral fossils of ancient germ line infections, reside within the human genome. Evidence of ERV activity has been observed widely in both health and disease. While this is most often cited as a bystander effect of cell culture or disease states, it is unclear which signals control ERV transcription. Bioinformatic analysis suggests that the viral promoter of endogenous retrovirus K (ERVK) is responsive to inflammatory transcription factors...
October 15, 2016: Journal of Virology
Iñaki Comas, Ana Gil
Tuberculosis (TB) has overtaken HIV (human immunodeficiency virus) and malaria as the leading cause of death by an infectious disease worldwide. The reduction in the TB incidence is a modest 2% of cases per year, thus we will need 200 years to eradicate the disease. Part of the problem is that TB control tools are decades old and cannot anymore contribute to accelerate eradication of TB. New diagnostics, treatments and vaccines are urgently needed. Next generation sequencing has the potential to become one of these new tools...
July 2016: Enfermedades Infecciosas y Microbiología Clínica
Ali Moghadam, Ali Niazi, Alireza Afsharifar, Seyed Mohsen Taghavi
In contrast to conventional antibiotics, which microorganisms can readily evade, it is nearly impossible for a microbial strain that is sensitive to antimicrobial proteins to convert to a resistant strain. Therefore, antimicrobial proteins and peptides that are promising alternative candidates for the control of bacterial infections are under investigation. The MAP30 protein of Momordica charantia is a valuable type I ribosome-inactivating protein (RIP) with anti-HIV and anti-tumor activities. Whereas the antimicrobial activity of some type I RIPs has been confirmed, less attention has been paid to the antimicrobial activity of MAP30 produced in a stable, easily handled, and extremely cost-effective protein-expression system...
2016: PloS One
Supreet Kaur Gill, Ajay Francis Christopher, Vikas Gupta, Parveen Bansal
Clinical research is making toiling efforts for promotion and wellbeing of the health status of the people. There is a rapid increase in number and severity of diseases like cancer, hepatitis, HIV etc, resulting in high morbidity and mortality. Clinical research involves drug discovery and development whereas clinical trials are performed to establish safety and efficacy of drugs. Drug discovery is a long process starting with the target identification, validation and lead optimization. This is followed by the preclinical trials, intensive clinical trials and eventually post marketing vigilance for drug safety...
July 2016: Perspectives in Clinical Research
Shambhu G Aralaguppe, Abu Bakar Siddik, Ashokkumar Manickam, Anoop T Ambikan, Milner M Kumar, Sunjay Jude Fernandes, Wondwossen Amogne, Dhinoth K Bangaruswamy, Luke Elizabeth Hanna, Anders Sonnerborg, Ujjwal Neogi
Analysing the HIV-1 near full-length genome (HIV-NFLG) facilitates new understanding into the diversity of virus population dynamics at individual or population level. In this study we developed a simple but high-throughput next generation sequencing (NGS) protocol for HIV-NFLG using clinical specimens and validated the method against an external quality control (EQC) panel. Clinical specimens (n=105) were obtained from three cohorts from two highly conserved HIV-1C epidemics (India and Ethiopia) and one diverse epidemic (Sweden)...
October 2016: Journal of Virological Methods
Qin Yan, Chenyou Shen, Jie Qin, Wan Li, Minmin Hu, Hongmei Lu, Di Qin, Jianzhong Zhu, Shou-Jiang Gao, Chun Lu
UNLABELLED: Kaposi's sarcoma-associated herpesvirus (KSHV) infection is required for the development of several AIDS-related malignancies, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). The high incidence of AIDS-KS has been ascribed to the interaction of KSHV and HIV-1. We have previously shown that HIV-1-secreted proteins Tat and Nef regulate the KSHV life cycle and synergize with KSHV oncogenes to promote angiogenesis and tumorigenesis. Here, we examined the regulation of KSHV latency by HIV-1 viral protein R (Vpr)...
October 1, 2016: Journal of Virology
Will Dampier, Gregory C Antell, Benjamas Aiamkitsumrit, Michael R Nonnemacher, Jeffrey M Jacobson, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Tony James, Kathryn N Devlin, Tania Giovannetti, David J Libon, Zsofia Szep, Garth D Ehrlich, Brian Wigdahl, Fred C Krebs
Even in the era of combination antiretroviral therapies used to combat human immunodeficiency virus type 1 (HIV-1) infection, up to 50 % of well-suppressed HIV-1-infected patients are still diagnosed with mild neurological deficits referred to as HIV-associated neurocognitive disorders (HAND). The multifactorial nature of HAND likely involves the HIV-1 accessory protein viral protein R (Vpr) as an agent of neuropathogenesis. To investigate the effect of naturally occurring variations in Vpr on HAND in well-suppressed HIV-1-infected patients, bioinformatic analyses were used to correlate peripheral blood-derived Vpr sequences with patient neurocognitive performance, as measured by comprehensive neuropsychological assessment and the resulting Global Deficit Score (GDS)...
July 11, 2016: Journal of Neurovirology
Ahmadreza Sadeghi, Elham Shirvani-Dastgerdi, Frank Tacke, Eray Yagmur, Vahdat Poortahmasebi, Mansour Poorebrahim, Minoo Mohraz, Mahboobeh Hajabdolbaghi, Mehrnaz Rasoolinejad, Ladan Abbasian, Rezvaneh Jafari, Zahra Fakhari, Mehdi Norouzi, Arefeh Ebrahimian, Babak Geravand, Seyed Moayed Alavian, Seyed Mohammad Jazayeri
BACKGROUND: Occult hepatitis B infection (OBI) is a frequent finding in human immunodeficiency virus (HIV)-infected patients. While several related mutations in the hepatitis B virus (HBV) genome have been reported, their distinct impact on HBsAg synthesis is largely obscure. METHODS: Thirty-one (18%) out of 172 HIV-infected patients, who were selected from HBsAg-negative patients, were positive for HBV-DNA assigned as being OBI-positive. We generated a series of expression constructs of variant HBsAg with "a" determinant amino acid substitutions including P127L, P127T, S136Y, and P127T + S136Y using site-directed mutagenesis...
February 2017: Journal of Medical Virology
Siddhartha Jain, Joel Arrais, Narasimhan J Venkatachari, Velpandi Ayyavoo, Ziv Bar-Joseph
MOTIVATION: Most methods for reconstructing response networks from high throughput data generate static models which cannot distinguish between early and late response stages. RESULTS: We present TimePath, a new method that integrates time series and static datasets to reconstruct dynamic models of host response to stimulus. TimePath uses an Integer Programming formulation to select a subset of pathways that, together, explain the observed dynamic responses. Applying TimePath to study human response to HIV-1 led to accurate reconstruction of several known regulatory and signaling pathways and to novel mechanistic insights...
June 15, 2016: Bioinformatics
Cinque Soto, Gilad Ofek, M Gordon Joyce, Baoshan Zhang, Krisha McKee, Nancy S Longo, Yongping Yang, Jinghe Huang, Robert Parks, Joshua Eudailey, Krissey E Lloyd, S Munir Alam, Barton F Haynes, James C Mullikin, Mark Connors, John R Mascola, Lawrence Shapiro, Peter D Kwong
Antibody 10E8 targets the membrane-proximal external region (MPER) of HIV-1 gp41, neutralizes >97% of HIV-1 isolates, and lacks the auto-reactivity often associated with MPER-directed antibodies. The developmental pathway of 10E8 might therefore serve as a promising template for vaccine design, but samples from time-of-infection-often used to infer the B cell record-are unavailable. In this study, we used crystallography, next-generation sequencing (NGS), and functional assessments to infer the 10E8 developmental pathway from a single time point...
2016: PloS One
Brett Williams, Paria Mirmonsef, Charles A B Boucher, Frederic Bushman, Stacy Carrington-Lawrence, Ronald G Collman, Satya Dandekar, Que Dang, Angela Malaspina, Roger Paredes, Arthur Stone, Alan Landay
The role of microbiota in the pathogenesis of HIV infection has become the subject of intense research in recent years. A rapidly growing amount of data suggests that microbial dysbiosis-in the gut or the genital tract-can influence HIV transmission and/or disease progression; however a deeper understanding of the mechanisms involved is lacking. To better understand the relationship between the microbiome and HIV infection, investigators from a wide variety of disciplines including those working in basic and clinical HIV studies, cardiovascular disease, reproductive health and bioinformatics gathered at the first International workshop on Microbiome in HIV Pathogenesis, Prevention and Treatment, at NIH on 7 and 8 April 2015...
June 7, 2016: AIDS Research and Human Retroviruses
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