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https://www.readbyqxmd.com/read/28803141/the-poly-proline-tail-of-sivmac-vpx-provides-gain-of-function-for-resistance-to-a-cryptic-proteasome-dependent-degradation-pathway
#1
Nannan Zhang, Haoran Guo, Jiaxin Yang, Guanchen Liu, Shuang Li, Siying Li, Dongyin Wang, Rui Li, Chang Shu, Hongmei Xu, Zhentong Wei, Honglan Huang, Songling Zhang, Pujun Gao, Shan Cen, Richard Markham, Yongsheng Wang, Xiao-Fang Yu, Wei Wei
The lentiviral accessory protein Vpx is critical for viral infection of myeloid cells and acts by hijacking CRL4(DCAF1) E3 ubiquitin ligase to induce the degradation of the host restriction factor SAMHD1. It has been observed that the sequences from HIV-2 and SIVsmm/SIVmac Vpx contain a poly-proline tail which is distinct from other SIV Vpx proteins. However, the role of this region in Vpx function is controversial. Herein, we found proteasome-dependent degradation of a Vpx mutant lacking the poly-proline tail in the nucleus in a CRL4(DCAF1) E3 ligase-independent fashion...
August 10, 2017: Virology
https://www.readbyqxmd.com/read/28800289/viral-master-circuits-from-discovery-to-new-therapy-targets
#2
Anand Pai, Leor S Weinberger
Current antivirals effectively target diverse viruses at various stages of their life cycles. Nevertheless, curative therapy has remained elusive for important pathogens, such as human immunodeficiency virus type 1 (HIV-1) and herpesviruses, in large part due to viral latency and the evolution of resistance to existing therapies. Here, we review the discovery of viral master circuits: virus-encoded autoregulatory gene networks that autonomously control viral expression programs (i.e., between active, latent, and abortive fates)...
August 11, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28796293/il7ra-polymorphisms-are-not-associated-with-aids-progression
#3
Luz María Medrano, José Luis Jiménez, María A Jiménez-Sousa, Amanda Fernández-Rodíguez, Mónica Gutiérrez-Rivas, José María Bellón, José Ramón Blanco, Alexy Inciarte, Mª Ángeles Muñoz-Fernández, Salvador Resino
BACKGROUND: Our aim was to determine whether α-chain of the IL-7 Receptor (IL7RA) polymorphisms (rs10491434, rs6897932, and rs987106) are associated with the clinical pattern of AIDS progression in ART-naïve HIV-infected patients. METHODS: We carried out a cross-sectional study in 673 HIV-infected patients who were classified into three groups according to the clinical pattern of AIDS progression (188 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 151 rapid progressors (RPs))...
August 10, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28794047/no-substantial-evidence-for-sexual-transmission-of-minority-hiv-drug-resistance-mutations-in-men-who-have-sex-with-men
#4
Antoine Chaillon, Masato Nakazawa, Joel O Wertheim, Susan J Little, Davey M Smith, Sanjay R Mehta, Sara Gianella
During primary HIV-infection, the presence of minority drug resistant mutations (DRM) may be a consequence of sexual transmission, de novo mutations or technical errors. Baseline blood samples were collected from 24 HIV-infected antiretroviral-naive, genetically- and epidemiologically- linked source and recipient partners, shortly after the recipient's estimated date of infection. An additional 32 longitudinal samples were available from 11 recipients. Deep-sequencing of HIV reverse transcriptase (RT) was performed (Roche/454) and screened for nucleoside and non-nucleoside RT inhibitor DRM...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28791125/nkg2c-memory-like-nk-cells-contribute-to-the-control-of-hiv-viremia-during-primary-infection-optiprim-anrs-147
#5
Françoise Gondois-Rey, Antoine Chéret, Samuel Granjeaud, Françoise Mallet, Ghislain Bidaut, Camille Lécuroux, Mickaël Ploquin, Michaela Müller-Trutwin, Christine Rouzioux, Véronique Avettand-Fenoël, Alessandro Moretta, Gilles Pialoux, Cécile Goujard, Laurence Meyer, Daniel Olive
Natural-killer (NK) cells are important immune effectors during a viral infection. Latent CMV infection is widely spread and was demonstrated to shape the NK cell repertoire through the NKG2C receptor. An expansion of NKG2C(+) NK cells has been reported during primary HIV infection (PHI), but their role is not known. We previously found a correlation between the maturation state of the NK cell compartment and a lower viral load by studying patients from the ANRS 147 Optiprim trial. We investigated here extensively the NKG2C(+) NK cells at the time of PHI and its evolution after 3 months of early antiretroviral therapy (combination antiretroviral therapy (cART))...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28765078/evolution-of-the-prevalence-of-hcv-infection-and-hcv-genotype-distribution-in-hiv-infected-patients-in-italy-between-1997-and-2015
#6
Barbara Rossetti, Francesca Bai, Alessandro Tavelli, Massimo Galli, Andrea Antinori, Francesco Castelli, Giampietro Pellizzer, Alessandro Cozzi-Lepri, Stefano Bonora, Antonella d'Arminio Monforte, Massimo Puoti, Andrea De Luca
OBJECTIVES: Aim of the study was to analyze the variation of HCV prevalence and genotype distribution and their determinants in people living with HIV who entered care between 1997 and 2015. METHODS: HIV-infected patients enrolled in ICONA who were tested for HCV-Antibodies (HCV-Ab) were included. RESULTS: Overall 3,407/12,135 (28.1%) were HCV-Ab+; and 735/12,135 (6.1%) were HBsAg+. Among patients whose HCV genotype was known, the most represented were genotype 1 and 3...
July 29, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28759651/rare-hiv-1-transmitted-founder-lineages-identified-by-deep-viral-sequencing-contribute-to-rapid-shifts-in-dominant-quasispecies-during-acute-and-early-infection
#7
Gustavo H Kijak, Eric Sanders-Buell, Agnes-Laurence Chenine, Michael A Eller, Nilu Goonetilleke, Rasmi Thomas, Sivan Leviyang, Elizabeth A Harbolick, Meera Bose, Phuc Pham, Celina Oropeza, Kultida Poltavee, Anne Marie O'Sullivan, Erik Billings, Melanie Merbah, Margaret C Costanzo, Joanna A Warren, Bonnie Slike, Hui Li, Kristina K Peachman, Will Fischer, Feng Gao, Claudia Cicala, James Arthos, Leigh A Eller, Robert J O'Connell, Samuel Sinei, Lucas Maganga, Hannah Kibuuka, Sorachai Nitayaphan, Mangala Rao, Mary A Marovich, Shelly J Krebs, Morgane Rolland, Bette T Korber, George M Shaw, Nelson L Michael, Merlin L Robb, Sodsai Tovanabutra, Jerome H Kim
In order to inform the rational design of HIV-1 preventive and cure interventions it is critical to understand the events occurring during acute HIV-1 infection (AHI). Using viral deep sequencing on six participants from the early capture acute infection RV217 cohort, we have studied HIV-1 evolution in plasma collected twice weekly during the first weeks following the advent of viremia. The analysis of infections established by multiple transmitted/founder (T/F) viruses revealed novel viral profiles that included: a) the low-level persistence of minor T/F variants, b) the rapid replacement of the major T/F by a minor T/F, and c) an initial expansion of the minor T/F followed by a quick collapse of the same minor T/F to low frequency...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28750322/longitudinal-sequencing-of-hiv-1-infected-patients-with-low-level-viremia-for-years-while-on-art-shows-no-indications-for-genetic-evolution-of-the-virus
#8
Leen Vancoillie, Laura Hebberecht, Kenny Dauwe, Els Demecheleer, Sylvie Dinakis, Dries Vaneechoutte, Virginie Mortier, Chris Verhofstede
HIV-infected patients on antiretroviral therapy (ART) may present low-level viremia (LLV) above the detection level of current viral load assays. In many cases LLV is persistent but does not result in overt treatment failure or selection of drug resistant viral variants. To elucidate whether LLV reflects active virus replication, we extensively sequenced pol and env genes of the viral populations present before and during LLV in 18 patients and searched for indications of genetic evolution. Maximum likelihood phylogenetic trees were inspected for temporal structure both visually and by linear regression analysis of root-to-tip and pairwise distances...
July 24, 2017: Virology
https://www.readbyqxmd.com/read/28750321/modeling-the-evolution-of-siv-sooty-mangabey-progenitor-virus-towards-hiv-2-using-humanized-mice
#9
Kimberly Schmitt, Dipu Mohan Kumar, James Curlin, Leila Remling-Mulder, Mark Stenglein, Shelby O'Connor, Preston Marx, Ramesh Akkina
HIV-2 is thought to have originated from an SIV progenitor native to sooty mangabeys. To model the initial human transmission and understand the sequential viral evolution, humanized mice were infected with SIVsm and serially passaged for five generations. Productive infection was seen by week 3 during the initial challenge followed by chronic viremia and gradual CD4(+) T cell decline. Viral loads increased by the 5th generation resulting in more rapid CD4(+) T cell decline. Genetic analysis revealed several amino acid substitutions that were nonsynonymous and fixed in multiple hu-mice across each of the 5 generations in the nef, env and rev regions...
July 24, 2017: Virology
https://www.readbyqxmd.com/read/28749251/identification-of-spirocyclic-or-phosphate-substituted-quinolizine-derivatives-as-novel-hiv-1-integrase-inhibitors-a-patent-evaluation-of-wo2016094197a1-wo2016094198a1-and-wo2016154527a1
#10
Xiqiang Cheng, Ping Gao, Lin Sun, Ye Tian, Peng Zhan, Xinyong Liu
Highly active antiretroviral therapy (HAART) has been widely adopted to control the HIV-1 infection successfully. HIV-1 integrase (IN) inhibitors are primary drugs in HAART regimens targeting integration step in the HIV-1 life cycle. However, due to the emergence of viral resistance and cross-resistance amongst drugs, there is a pressing need for new and potent IN inhibitors. This review covers the three patents describing spirocyclic and phosphate substituted quinolizine derivatives as novel HIV-1 IN inhibitors for the discovery of new anti-HIV-1 drug candidates...
July 27, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28747059/rectal-inflammatory-stenosis-secondary-to-chlamydia-trachomatis-a-case-report
#11
Luis Eduardo Pérez Sánchez, Moisés Hernández Barroso, Guillermo Hernández Hernández
The rectal inflammatory originated strictures constitute a rare cause of intestinal obstruction. We present a 30-year-old male patient with a history of HIV and protctitis caused by Chalmydia trachomatis and HSV-2, in which develops a low intestinal obstruction refractory to medical treatment. Surgery was performed with good clinical evolution. The medical treatment constitutes the fundamental basis of the therapy in these patients. Despite that, when fibrotic stenoses are not treatable medical or endoscopically, they often require surgical treatment...
July 27, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28739269/extracutaneous-atypical-syphilis-in-hiv-infected-patients
#12
Paula Prieto, Arkaitz Imaz, Laura Calatayud, Olga García, María Saumoy, Daniel Podzamczer
INTRODUCTION AND OBJETIVE: We describe a series of cases of syphilis with atypical extracutaneous clinical presentation diagnosed in HIV-infected patients. METHODS: Retrospective observational study. All cases of syphilis diagnosed in HIV-infected patients during the period between June 2013 and June 2016 in a tertiary hospital of the Barcelona metropolitan area were analysed. RESULTS: A total of 71 cases of syphilis were diagnosed, 32 of them presenting with clinical signs or symptoms...
July 21, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28730408/evolution-of-the-hiv-1-transgenic-rat-utility-in-assessing-the-progression-of-hiv-1-associated-neurocognitive-disorders
#13
Kristen A McLaurin, Rosemarie M Booze, Charles F Mactutus
Understanding the progression of HIV-1-associated neurocognitive disorders (HAND) is a critical need as the prevalence of HIV-1 in older individuals (>50 years) is markedly increasing due to the great success of combination antiretroviral therapy (cART). Longitudinal experimental designs, in comparison to cross-sectional studies, provide an opportunity to establish age-related disease progression in HAND. The HIV-1 transgenic (Tg) rat, which has been promoted for investigating the effect of long-term HIV-1 viral protein exposure, was used to examine two interrelated goals...
July 20, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28705757/social-support-in-newly-diagnosed-people-living-with-hiv-expectations-and-satisfaction-along-time-predictors-and-mental-health-correlates
#14
Helena Garrido-Hernansaiz, Jesús Alonso-Tapia
Social support usually decreases following HIV diagnosis, and decreased support is related to worsening mental health. We investigated the evolution of social support after HIV diagnosis and its relationship to anxiety, depression, and resilience, and sought to develop a social support prediction model. There were 119 newly diagnosed Spanish speakers who participated in this longitudinal study, completing measures of social support, internalized stigma, disclosure concerns, degree of disclosure, coping, anxiety, depression, and resilience...
June 19, 2017: Journal of the Association of Nurses in AIDS Care: JANAC
https://www.readbyqxmd.com/read/28705278/history-of-seborrheic-dermatitis-conceptual-and-clinico-pathologic-evolution
#15
REVIEW
Angela Cristina Akel Mameri, Sueli Carneiro, Letícia Maria Akel Mameri, José Marcos Telles da Cunha, Marcia Ramos-E-Silva
Seborrheic dermatitis is an inflammatory and chronic disease with a high incidence and prevalence (1% to 3% in the general population, 3% to 5% in young adults, and 40% to 80% in HIV-positive individuals). Although the condition was first described in 1887, its clinical aspects and clinical forms have still not been well individualized, nor has its etiopathogenesis been fully elucidated. The disease, despite having clinical features similar to dermatitis, does not have the same histopathologic features or the same progressive clinical behavior...
2017: Skinmed
https://www.readbyqxmd.com/read/28696188/evolution-of-cross-neutralizing-antibodies-and-mapping-epitope-specificity-in-plasma-of-chronic-hiv-1-infected-antiretroviral-therapy-na%C3%A3-ve-children-from-india
#16
Muzamil A Makhdoomi, Lubina Khan, Sanjeev Kumar, Heena Aggarwal, Ravinder Singh, Rakesh Lodha, Mohit Singla, Bimal K Das, Sushil K Kabra, Kalpana Luthra
Delineating the factors leading to the development of broadly neutralizing antibodies (bnAbs) during natural HIV-1 infection and dissecting their epitope specificities generates useful information for vaccine design. This is the first longitudinal study to assess the plasma-neutralizing antibody response and neutralizing determinants in HIV-1-infected children from India. We enrolled 26 and followed up 20 antiretroviral therapy (ART)-naïve, asymptomatic, chronic HIV-1-infected children. Five (19.2 %) baseline and 10 (50 %) follow-up plasma samples neutralized ≥50 % of subtypes A, B and C tier 2 viruses at an ID50 titre ≥150...
July 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28692659/lesbian-gay-bisexual-and-transgender-lgbt-health-services-in-the-united-states-origins-evolution-and-contemporary-landscape
#17
Alexander J Martos, Patrick A Wilson, Ilan H Meyer
BACKGROUND: LGBT community organizations in the United States have been providing health services since at least the 1970s. However, available explanations for the origins of LGBT health services do not sufficiently explain why health in particular has been so closely and consistently linked to LGBT activism. Little is also known regarding how LGBT health services may have evolved over time with the growing scientific understanding of LGBT health needs. METHODS: This study begins with a review of the early intersections of sexuality and health that led to an LGBT health movement in the United States, as well as the evolution of LGBT health services over time...
2017: PloS One
https://www.readbyqxmd.com/read/28685417/the-lymph-node-in-hiv-pathogenesis
#18
REVIEW
Yiannis Dimopoulos, Eirini Moysi, Constantinos Petrovas
Lymph nodes play a central role in the development of adaptive immunity against pathogens and particularly the generation of antigen-specific B cell responses in specialized areas called germinal centers (GCs). Lymph node (LN) pathology was recognized as an important consequence of human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. Investigation into the structural and functional alterations induced by HIV and Simian immunodeficiency virus (SIV) has further cemented the central role that lymphoid tissue plays in HIV/SIV pathogenesis...
July 7, 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28679760/co-operation-between-strain-specific-and-broadly-neutralizing-responses-limited-viral-escape-and-prolonged-exposure-of-the-broadly-neutralizing-epitope
#19
Colin Anthony, Talita York, Valerie Bekker, David Matten, Philippe Selhorst, Roux-Cil Ferreria, Nigel J Garrett, Salim S Abdool Karim, Lynn Morris, Natasha T Wood, Penny L Moore, Carolyn Williamson
V3-glycan targeting broadly neutralizing antibodies (bNAbs) are a focus of HIV-1 vaccine development. Understanding the viral dynamics that stimulate the development of these antibodies can provide insights for immunogen design. We used a deep sequencing approach, together with neutralization phenotyping, to investigate the rate and complexity of escape from V3-glycan directed bNAbs, compared to overlapping early strain-specific neutralizing antibody (ssNAb) responses to the V3/C3 region in donor CAP177. Escape from the ssNAb response occurred rapidly, via a N334 to N332 glycan switch, which took just 7...
July 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28670581/mutant-cas9-transcriptional-activator-activates-hiv-1-in-u1-cells-in-the-presence-and-absence-of-ltr-specific-guide-rnas
#20
Veronica Kim, Brian M Mears, Bonita H Powell, Kenneth W Witwer
CRISPR/Cas9 systems have been advanced as promising tools in the HIV eradication armamentarium for sequence-specific disruption or latency reversal. Enthusiasm is balanced by concerns about off-target host genome modification and effects on HIV evolution. In the chronically HIV-1-infected U1 promonocytic latency model, we have confirmed stimulation of HIV-1 production by a mutant Cas9-transcriptional activator and guide RNAs with two guide RNAs apparently more potent than one. However, significant increases were also observed in the absence of guide RNAs...
2017: Matters (Zur)
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