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Hiv entry

Jeanne M Sisk, Matthew B Frieman, Carolyn E Machamer
Enveloped viruses gain entry into host cells by fusing with cellular membranes, a step that is required for virus replication. Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and infectious bronchitis virus (IBV), fuse at the plasma membrane or use receptor-mediated endocytosis and fuse with endosomes, depending on the cell or tissue type. The virus spike (S) protein mediates fusion with the host cell membrane. We have shown previously that an Abelson (Abl) kinase inhibitor, imatinib, significantly reduces SARS-CoV and MERS-CoV viral titres and prevents endosomal entry by HIV SARS S and MERS S pseudotyped virions...
March 20, 2018: Journal of General Virology
Ferdinand Roesch, Molly OhAinle, Michael Emerman
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 viruses. Some lentiviruses evolved Vpx/Vpr proteins to degrade SAMHD1. However, this viral antagonism can be perturbed by host mechanisms: a recent study showed that in interferon (IFN) treated THP1 cells, Vpx is unable to degrade SAMHD1. In the present work, we designed an Interferon Stimulated Genes (ISGs)-targeted CRISPR knockout screen in order to identify ISGs regulating this phenotype...
March 20, 2018: Retrovirology
Hannah F Löchel, Mona Riemenschneider, Dmitrij Frishman, Dominik Heider
Motivation: The V3 loop of the gp120 glycoprotein of the Human Immunodeficiency Virus 1 (HIV-1) is considered to be responsible for viral coreceptor tropism. gp120 interacts with the CD4 receptor of the host cell and subsequently V3 binds either CCR5 or CXCR4. Due to the fact that the CCR5 coreceptor is targeted by entry inhibitors, a reliable prediction of the coreceptor usage of HIV-1 is of great interest for antiretroviral therapy. Although several methods for the prediction of coreceptor tropism are available, almost all of them have been developed based on only subtype B sequences, and it has been shown in several studies that the prediction of non-B sequences, in particular subtype A sequences, are less reliable...
March 15, 2018: Bioinformatics
S E M van Opstal, J S van der Zwan, M N Wagener, S K Been, H S Miedema, P D D M Roelofs, E C M van Gorp
Late diagnosis of HIV remains a major challenge in the HIV epidemic. In Europe, about 50% of all people living with HIV are diagnosed late after infection has occurred. Insight into the reasons for late diagnoses is necessary to increase the number of early diagnoses and optimize treatment options. This qualitative study explored the experiences of 34 late-presenters through in-depth semi-structured interviews. A variety of reasons for late diagnoses emerged from our data and led to a division into four groups, characterized by two dimensions...
March 17, 2018: AIDS and Behavior
Jie Yu, Yaoming Li, Maohua Zhong, Jingyi Yang, Dihan Zhou, Bali Zhao, Yuan Cao, Hu Yan, Ejuan Zhang, Yi Yang, Zhengshan Feng, Xiuwen Qi, Huimin Yan
The development of an effective HIV-1 vaccine is still a global priority. In recent years, vaccinia virus (VV) has been widely used as an HIV-1 vaccine vector, but its immune efficacy against HIV-1 antigens needs to be optimized. The extracellular enveloped virus (EEV) of VV is capable of faster entry, earlier release, and long-range dissemination. We hypothesized that an improvement in EEV formation by the manipulation of VV genes involved in the EEV release would consequently cause an improved expression of the VV carrying HIV-1 Env antigen and a subsequent enhanced immune response...
March 14, 2018: Antiviral Research
Yibeltal Assefa, Peter S Hill, Owain D Williams
At September's 2017 United Nations General Assembly, a state-of-the-art HIV medicine was announced to be made available at just $75 per person per year. There have been a number of strategies that the global AIDS community and countries have utilized to reduce prices and make antiretrovirals (ARVs) accessible for people living with HIV/AIDS. There appears to be an opportunity for the treatment of hepatitis C virus infection using direct-acting antivirals (DAAs) to benefit from the often painful and laboured history of driving down the prices of ARVs...
March 14, 2018: International Journal of Infectious Diseases: IJID
Kristen A Stafford, Lucy W Nganga, Tuhuma Tulli, Karen G Fleischman Foreit
The World Health Organization recommended removing all CD4 requirements for initiation of antiretroviral therapy (ART) in resource-limited settings. We examined the pre-ART period to identify and assess factors associated with outcomes of pre-ART care. Four modes of transition out of pre-ART care were considered. Beta estimates from the competing risks Cox models were used to investigate whether the effects of covariates differed by mode of transition. Median CD4 counts at entry showed no meaningful change over time...
January 2018: Journal of the International Association of Providers of AIDS Care
R Modi, K R Amico, A Knudson, A O Westfall, J Keruly, H M Crane, E B Quinlivan, C Golin, J Willig, A Zinski, R Moore, S Napravnik, L Bryan, M S Saag, M J Mugavero
In the first year after HIV diagnosis, patients are simultaneously processing with their diagnosis, typically with an emotional component, while also developing a routine of regular medical care visits and antiretroviral therapy (ART) adherence. Maintaining "HIV adherence" and integrating it into one's daily life is required to sustain viral load suppression (VS) over time. The HIV care continuum or "treatment cascade," an epidemiological snapshot of the national epidemic in the United States (US), indicates that a minority of persons living with HIV (PLWH) have achieved VS...
March 8, 2018: Contemporary Clinical Trials
Anvita Bhargava, Xavier Lahaye, Nicolas Manel
The nuclear envelope is a physical barrier that isolates the cellular DNA from the rest of the cell, thereby limiting pathogen invasion. The Human Immunodeficiency Virus (HIV) has a remarkable ability to enter the nucleus of non-dividing target cells such as lymphocytes, macrophages and dendritic cells. While this step is critical for replication of the virus, it remains one of the less understood aspects of HIV infection. Here, we review the viral and host factors that favor or inhibit HIV entry into the nucleus, including the viral capsid, integrase, the central viral DNA flap, and the host proteins CPSF6, TNPO3, Nucleoporins, SUN1, SUN2, Cyclophilin A and MX2...
February 27, 2018: Cytokine & Growth Factor Reviews
Nitesh Mishra, Madhav Mohata, Heena Aggarwal, Omkar Chaudhary, Bimal Kumar Das, Sanjeev Sinha, Anjali Hazarika, Kalpana Luthra
During infection and budding, human immunodeficiency virus-1 (HIV-1) acquires regulators of Complement Activation (RCAs) along with the host cell membrane on the viral envelope. Activation of host complement system results in opsonization of virus by complement fragments, however the virus evades complement mediated lysis (CoML) by virtue of the RCAs on the viral envelope. The RCAs on HIV-1 envelope process complement protein C3 into various fragments that promote viral entry and infection of cells through different complement receptors...
March 7, 2018: Molecular Immunology
Wenwen Dai, Yu Wu, Jinpeng Bi, Shuai Wang, Fang Li, Wei Kong, Julien Barbier, Jean-Christophe Cintrat, Feng Gao, Daniel Gillet, Weiheng Su, Chunlai Jiang
Herpes simplex virus type 2 (HSV-2) is the causative pathogen of genital herpes and is closely associated with the occurrence of cervical cancer and human immunodeficiency virus (HIV) infection. The absence of an effective vaccine and the emergence of drug resistance to commonly used nucleoside analogs emphasize the urgent need for alternative antivirals against HSV-2. Recently, ABMA [1-adamantyl (5-bromo-2-methoxybenzyl) amine] has been demonstrated to be an inhibitor of several pathogens exploiting host-vesicle transport, which also participates in the HSV-2 lifecycle...
March 9, 2018: Viruses
M M Jamil Al-Obaidi, A Bahadoran, S M Wang, R Manikam, Ch S Raju, S D Sekaran
The blood brain barrier consisting of astrocytes, pericytes and brain microvascular endothelial cells plays a vital role in the pathogenesis of neurotropic viruses by controlling the access of circulating molecules, immune cells or viruses into the central nervous system (CNS). However, this barrier is not impenetrable and neuroviruses have evolved to disrupt and evade it. This review aims to describe the underlying entry mechanisms of several neuroviruses such as (Japanese encephalitis virus (JEV), West Nile virus (WNV), Zika virus (ZIKV), Nipah virus (NiV), Rabies virus (RABV), Herpes simplex virus (HSV) and Human immunodeficiency virus (HIV)) into the CNS through BBB disruption...
2018: Acta Virologica
Nicholas R Meyerson, Cody J Warren, Daniel A S A Vieira, Felipe Diaz-Griferro, Sara L Sawyer
HIV-1 arose as the result of spillover of simian immunodeficiency viruses (SIVs) from great apes in Africa, namely from chimpanzees and gorillas. Chimpanzees and gorillas were, themselves, infected with SIV after virus spillover from African monkeys. During spillover events, SIV is thought to require adaptation to the new host species. The host barriers that drive viral adaptation have predominantly been attributed to restriction factors, rather than cofactors (host proteins exploited to promote viral replication)...
March 2018: PLoS Pathogens
Le Guo, Xi-Qiu Xu, Li Zhou, Run-Hong Zhou, Xu Wang, Jie-Liang Li, Jin-Biao Liu, Hang Liu, Biao Zhang, Wen-Zhe Ho
As a rich source of CD4+ T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI-resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we investigated whether human IECs have the ability to produce antiviral factors that can inhibit HIV infection of macrophages. We demonstrated that IECs possess functional toll-like receptor 3 (TLR3), the activation of which resulted in induction of key interferon (IFN) regulatory factors (IRF3 and IRF7), IFN-β, IFN-λ, and CC chemokines (MIP-1α, MIP-1β, RANTES), the ligands of HIV entry co-receptor CCR5...
2018: Frontiers in Immunology
Savrina Manhas, Lina Ma, Vivien Measday
Nuclear pore complexes (NPCs) orchestrate cargo between the cytoplasm and nucleus and regulate chromatin organization. NPC proteins, or nucleoporins (Nups), are required for human immunodeficiency virus type 1 (HIV-1) gene expression and genomic integration of viral DNA. We utilize the Ty1 retrotransposon of Saccharomyces cerevisiae (S. cerevisiae) to study retroviral integration because retrotransposons are the progenitors of retroviruses and have conserved integrase (IN) enzymes. Ty1-IN targets Ty1 elements into the genome upstream of RNA polymerase (Pol) III transcribed genes such as transfer RNA (tRNA) genes...
March 5, 2018: Nucleic Acids Research
Sergio Carmona, Jacob Bor, Cornelius Nattey, Brendan Maughan-Brown, Mhairi Maskew, Matthew P Fox, Deborah K Glencross, Nathan Ford, William B MacLeod
Background: The South African national HIV program has increased antiretroviral therapy (ART) coverage over the last decade, supported by policy changes allowing for earlier ART initiation. However, many patients still enter care with advanced (<200 cells/μL) and very advanced (<100 cells/μL) HIV disease. We assessed disease progression at entry to care using nationwide laboratory data. Methods: We constructed a national HIV cohort using laboratory records containing HIV RNA loads and CD4 counts from 2004 to 2016 to determine entry into care...
March 4, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Y Grégoire, M Germain, G Delage
BACKGROUND AND OBJECTIVES: Since 25 May 2010, all donors at our blood centre who tested false-positive for HIV, HBV, HCV or syphilis are eligible for re-entry after further testing. Donors who have a second false-positive screening test, either during qualification for or after re-entry, are deferred for life. This study reports on factors associated with the occurrence of such deferrals. MATERIALS AND METHODS: Rates of second false-positive results were compared by year of deferral, transmissible disease marker, gender, age, donor status (new or repeat) and testing platform (same or different) both at qualification for re-entry and afterwards...
March 6, 2018: Vox Sanguinis
Dian Peng, Bin Cao, Ying-Jun Zhou, Ya-Qiu Long
The CXC chemokine receptor 4 (CXCR4) is a highly reserved G-protein coupled 7-transmembrane (TM) chemokine receptor which consists of 352 amino acids. CXCR4 has only one endogenous chemokine ligand of CXCL12, besides several other natural nonchemokine ligands such as extracellular ubiquitin and noncognate ligand of MIF. CXCR4 strongly binds to CXCL12 and the resulting CXCLl2/CXCR4 axis is the molecular basis of their various biological functions, which include: (1) mediating immune and inflammatory response; (2) regulation of hematopoietic stem cell migration and homing; (3) an essential co-receptor for HIV entry into host cells; (4) participation in the process of embryonic development; (5) malignant tumor invasion and metastasis; (6) myocardial infarction, ischemic stroke and acute kidney injury...
February 17, 2018: European Journal of Medicinal Chemistry
Frank-Leonel Tianyi, Joel Noutakdie Tochie, Valirie Ndip Agbor, Benjamin Momo Kadia
INTRODUCTION: HIV testing is an invaluable entry point to prevention, care and treatment services for people living with HIV and AIDS. Poor adherence to recommended protocols and guidelines reduces the performance of rapid diagnostic tests, leading to misdiagnosis and poor estimation of HIV seroprevalence. This study seeks to evaluate the adherence of primary healthcare facilities in Cameroon to recommended HIV counselling and testing (HCT) procedures and the impact this may have on the reliability of HIV test results...
March 1, 2018: BMJ Open
Minjun Yang, Ruina Zhi, Lu Lu, Mingxin Dong, Yuzhu Wang, Fang Tian, Minjie Xia, Jingying Hu, Qiuyun Dai, Shibo Jiang, Weihua Li
B07 is a small-molecule CCR5 antagonist-based HIV-1 entry inhibitor that is being developed as an anti-HIV microbicide for preventing sexual transmission of HIV. Here we evaluated its spermicidal and contraceptive potential, including sperm motility, plasma membrane integrity, and contraceptive efficacy tested in rabbits. We found that B07 inhibited sperm motility and movement patterns in a concentration- and time-dependent manner. Within 30 min, B07 induced sperm immobilization with the minimum 100% effective concentration and median effective concentration of 640...
February 26, 2018: European Journal of Pharmaceutical Sciences
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