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https://www.readbyqxmd.com/read/27906032/infection-of-rhesus-macaques-with-a-pool-of-simian-immunodeficiency-virus-with-the-envelope-genes-from-acute-hiv-1-infections
#1
Kendall C Krebs, Meijuan Tian, Mohammed Asmal, Binhua Ling, Kenneth Nelson, Kenneth Henry, Richard Gibson, Yuejin Li, Weining Han, Robin J Shattock, Ronald S Veazey, Norman Letvin, Eric J Arts, Yong Gao
BACKGROUND: New simian-human immunodeficiency chimeric viruses with an HIV-1 env (SHIVenv) are critical for studies on HIV pathogenesis, vaccine development, and microbicide testing. Macaques are typically exposed to single CCR5-using SHIVenv which in most instances does not reflect the conditions during acute/early HIV infection (AHI) in humans. Instead of individual and serial testing new SHIV constructs, a pool of SHIVenv_B derived from 16 acute HIV-1 infections were constructed using a novel yeast-based SHIV cloning approach and then used to infect macaques...
November 25, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27905985/tlr7-8-agonist-induces-a-post-entry-samhd1-independent-block-to-hiv-1-infection-of-monocytes
#2
Henning Hofmann, Bénédicte Vanwalscappel, Nicolin Bloch, Nathaniel R Landau
BACKGROUND: Monocytes, the primary myeloid cell-type in peripheral blood, are resistant to HIV-1 infection as a result of the lentiviral restriction factor SAMHD1. Toll-like receptors recognize microbial pathogen components, inducing the expression of antiviral host proteins and proinflammatory cytokines. TLR agonists that mimic microbial ligands have been found to have activity against HIV-1 in macrophages. The induction of restriction factors in monocytes by TLR agonist activation has not been well studied...
December 1, 2016: Retrovirology
https://www.readbyqxmd.com/read/27905841/cell-delivered-entry-inhibitors-for-hiv-1-ccr5-downregulation-and-blocking-virus-membrane-fusion-in-defending-the-host-cell-population
#3
Geoff Symonds, Jeffrey S Bartlett, Hans-Peter Kiem, Marlene Tsie, Louis Breton
HIV-1 infection requires the presence of the CD4 receptor on the target cell surface and a coreceptor, predominantly CC-chemokine receptor 5 (CCR5). It has been shown that individuals who are homozygous for a defective CCR5 gene are protected from HIV-1 infection. A novel self-inactivating lentiviral vector LVsh5/C46 (Cal-1) has been engineered to block HIV-1 infection with two viral entry inhibitors, conferring resistance to HIV-1 infection from both CCR5 and CXCR4 tropic strains. Cal-1 encodes a short hairpin RNA (sh5) to downregulate CCR5 and C46, an HIV-1 fusion inhibitor...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27903799/cxcr6-mediated-sivagmsab-entry-into-sabaeus-african-green-monkey-lymphocytes-implicates-widespread-use-of-non-ccr5-pathways-in-natural-host-infections
#4
Katherine S Wetzel, Yanjie Yi, Sarah T C Elliott, Dino Romero, Beatrice Jacquelin, Beatrice H Hahn, Michaela Muller-Trutwin, Cristian Apetrei, Ivona Pandrea, Ronald G Collman
: African green monkeys (AGM) and sooty mangabeys (SM) are well-studied natural hosts of SIV, which do not progress to AIDS when infected with their species-specific viruses. SIV natural hosts express very low levels of the canonical entry coreceptor CCR5, and recent studies have shown that CCR5 is dispensable for SIV infection of SM in vivo, and blocking CCR5 does not prevent ex vivo infection of PBMC from SM or vervet AGM. In both hosts, CXCR6 is an efficient entry pathway in vitro...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27881659/glycosyl-phosphatidylinositol-gpi-anchored-anti-hiv-scfv-efficiently-protect-cd4-t-cells-from-hiv-1-infection-and-deletion-in-hu-pbl-mice
#5
Chaobaihui Ye, Weiming Wang, Liang Cheng, Guangming Li, Michael Wen, Qi Wang, Qing Zhang, Dan Li, Paul Zhou, Lishan Su
: Despite the success in viral inhibition and CD4 T cell recovery by highly active antiretroviral treatment (HAART), HIV-1 is still not curable due to the persistence of HIV-1 reservoir during treatment. One patient with acute myeloid leukemia who received allogeneic hematopoietic stem cell transplantation from homozygous CCR5 Δ32 donor has had no detectable viremia for 9 years after HAART cessation. This case has inspired a field of HIV-1 cure research focusing on engineering HIV-1 resistance of permissive cells...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27881646/activation-and-inactivation-of-primary-human-immunodeficiency-virus-hiv-1-envelope-glycoprotein-trimers-by-cd4-mimetic-compounds
#6
Navid Madani, Amy M Princiotto, Connie Zhao, Fatemeh Jahanbakhshsefidi, Max Mertens, Alon Herschhorn, Bruno Melillo, Amos B Smith, Joseph Sodroski
: Human immunodeficiency virus (HIV-1) entry into cells is mediated by the viral envelope glycoproteins (Env), a trimer of three gp120 exterior glycoproteins and three gp41 transmembrane glycoproteins. The metastable Env is triggered to undergo entry-related conformational changes when gp120 binds sequentially to the receptors, CD4 and CCR5, on the target cell. Small-molecule CD4-mimetic compounds (CD4mc) bind gp120 and act as competitive inhibitors of gp120-CD4 engagement. Some CD4mc have been shown to trigger Env prematurely, initially activating Env function, followed by rapid and irreversible inactivation...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27879338/functional-interplay-between-murine-leukemia-virus-glycogag-serinc5-and-surface-glycoprotein-governs-virus-entry-with-opposite-effects-on-gammaretroviral-and-ebolavirus-glycoproteins
#7
Yadvinder S Ahi, Shu Zhang, Yashna Thappeta, Audrey Denman, Amin Feizpour, Suryaram Gummuluru, Bjoern Reinhard, Delphine Muriaux, Matthew J Fivash, Alan Rein
: Gammaretroviruses, such as murine leukemia viruses (MLVs), encode, in addition to the canonical Gag, Pol, and Env proteins that will form progeny virus particles, a protein called "glycogag" (glycosylated Gag). MLV glycogag contains the entire Gag sequence plus an 88-residue N-terminal extension. It has recently been reported that glycogag, like the Nef protein of HIV-1, counteracts the antiviral effects of the cellular protein Serinc5. We have found, in agreement with prior work, that glycogag strongly enhances the infectivity of MLVs with some Env proteins but not those with others...
November 22, 2016: MBio
https://www.readbyqxmd.com/read/27876849/characterization-of-two-distinct-early-post-entry-blocks-to-hiv-1-in-common-marmoset-lymphocytes
#8
Beatriz Pacheco, Luis Menéndez-Arias, Joseph Sodroski
In nature, primate lentiviruses infect humans and several Old World monkeys and apes. However, to date, lentiviruses infecting New World monkeys have not been described. We studied the susceptibility of common marmoset cells to HIV-1 infection and observed the presence of post-entry blocks to the early phase of HIV-1 infection in peripheral blood lymphocytes (PBLs) and a B lymphocytic cell line (B-LCL). The blocks present in these cells are dominant and phenotypically different from each other. In PBLs, the block occurs at the level of reverse transcription, reducing the accumulation of early and late transcripts, similar to the block imposed by TRIM5α...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27875993/a-transcriptome-based-model-of-central-memory-cd4-t-cell-death-in-hiv-infection
#9
Gustavo Olvera-García, Tania Aguilar-García, Fany Gutiérrez-Jasso, Iván Imaz-Rosshandler, Claudia Rangel-Escareño, Lorena Orozco, Irma Aguilar-Delfín, Joel A Vázquez-Pérez, Joaquín Zúñiga, Santiago Pérez-Patrigeon, Enrique Espinosa
BACKGROUND: Human central memory CD4 T cells are characterized by their capacity of proliferation and differentiation into effector memory CD4 T cells. Homeostasis of central memory CD4 T cells is considered a key factor sustaining the asymptomatic stage of Human Immunodeficiency Virus type 1 (HIV-1) infection, while progression to acquired immunodeficiency syndrome is imputed to central memory CD4 T cells homeostatic failure. We investigated if central memory CD4 T cells from patients with HIV-1 infection have a gene expression profile impeding proliferation and survival, despite their activated state...
November 22, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27858872/physical-fitness-characteristics-of-active-duty-us-air-force-members-with-hiv-infection
#10
Asha De, Xiaohe Xu, James White, Thankam S Sunil, Jason F Okulicz
Human immunodeficiency virus (HIV) infection is associated with reduced muscle mass and adverse metabolic effects. We evaluated the impact of HIV infection on longitudinal exercise performance in US Air Force (USAF) members with HIV infection.USAF members perform standardized fitness assessments every 6 to 12 months with a composite score comprised of abdominal circumference, push-ups, sit-ups, and 1.5-mile run. Fitness tests between 2004 and 2014 for male USAF members with HIV infection (n = 172) were compared with male HIV-negative controls (∼10 per case; n = 1636) matched by age and rank category at service entry...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27855210/potent-and-broad-inhibition-of-hiv-1-by-a-peptide-from-the-gp41-heptad-repeat-2-domain-conjugated-to-the-cxcr4-amino-terminus
#11
George J Leslie, Jianbin Wang, Max W Richardson, Beth S Haggarty, Kevin L Hua, Jennifer Duong, Anthony J Secreto, Andrea P O Jordon, Josephine Romano, Kritika E Kumar, Joshua J DeClercq, Philip D Gregory, Carl H June, Michael J Root, James L Riley, Michael C Holmes, James A Hoxie
HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27843825/drug-adherence-rate-and-loss-to-follow-up-among-people-living-with-hiv-aids-attending-an-art-centre-in-a-tertiary-government-hospital-in-western-india
#12
Kedar G Mehta, Rajendra Baxi, Sangita Patel, Mahendra Parmar
INTRODUCTION: National AIDS Control Organization (NACO) has expanded the reach of anti retroviral therapy (ART) to combat the epidemic of HIV/AIDS in India which has one of the largest populations of people living with HIV/AIDS (PLWHA) in the world. One of the major challenges related to ART is a lifelong commitment by patients to adhere diligently to daily medication dosing schedules and scheduled visits to the ART center. Hence, the current study is carried out to assess the drug adherence rate and loss to follow-up (LFU) among PLWHA attending ART centre of a tertiary care hospital in Western India...
April 2016: Journal of Family Medicine and Primary Care
https://www.readbyqxmd.com/read/27830755/dynamic-oligomerization-of-integrase-orchestrates-hiv-nuclear-entry
#13
Doortje Borrenberghs, Lieve Dirix, Flore De Wit, Susana Rocha, Jolien Blokken, Stéphanie De Houwer, Rik Gijsbers, Frauke Christ, Johan Hofkens, Jelle Hendrix, Zeger Debyser
Nuclear entry is a selective, dynamic process granting the HIV-1 pre-integration complex (PIC) access to the chromatin. Classical analysis of nuclear entry of heterogeneous viral particles only yields averaged information. We now have employed single-virus fluorescence methods to follow the fate of single viral pre-integration complexes (PICs) during infection by visualizing HIV-1 integrase (IN). Nuclear entry is associated with a reduction in the number of IN molecules in the complexes while the interaction with LEDGF/p75 enhances IN oligomerization in the nucleus...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27820858/saturation-mutagenesis-of-the-hiv-1-envelope-cd4-binding-loop-reveals-residues-controlling-distinct-trimer-conformations
#14
Maria Duenas-Decamp, Li Jiang, Daniel Bolon, Paul R Clapham
The conformation of HIV-1 envelope (Env) glycoprotein trimers is key in ensuring protection against waves of neutralizing antibodies generated during infection, while maintaining sufficient exposure of the CD4 binding site (CD4bs) for viral entry. The CD4 binding loop on Env is an early contact site for CD4 while penetration of a proximal cavity by CD4 triggers Env conformational changes for entry. The role of residues in the CD4 binding loop in regulating the conformation of the trimer and trimer association domain (TAD) was investigated using a novel saturation mutagenesis approach...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27814706/testing-a-counselling-intervention-in-antenatal-care-for-women-experiencing-partner-violence-a-study-protocol-for-a-randomized-controlled-trial-in-johannesburg-south-africa
#15
Christina Pallitto, Claudia García-Moreno, Heidi Stöeckl, Abigail Hatcher, Catherine MacPhail, Keneoue Mokoatle, Nataly Woollett
BACKGROUND: Intimate partner violence (IPV) during or before pregnancy is associated with many adverse health outcomes. Pregnancy-related complications or poor infant health outcomes can arise from direct trauma as well as physiological effects of stress, both of which impact maternal health and fetal growth and development. Antenatal care can be a key entry point within the health system for many women, particularly in low-resource settings. Interventions to identify violence during pregnancy and offer women support and counselling may reduce the occurrence of violence and mitigate its consequences...
November 5, 2016: BMC Health Services Research
https://www.readbyqxmd.com/read/27812166/survival-outcomes-in-a-pediatric-antiretroviral-treatment-cohort-in-southern-malawi
#16
Jason C Brophy, Michael T Hawkes, Edson Mwinjiwa, Gabriel Mateyu, Sumeet K Sodhi, Adrienne K Chan
BACKGROUND: Pediatric uptake and outcomes in antiretroviral treatment (ART) programmes have lagged behind adult programmes. We describe outcomes from a population-based pediatric ART cohort in rural southern Malawi. METHODS: Data were analyzed on children who initiated ART from October/2003 -September/2011. Demographics and diagnoses were described and survival analyses conducted to assess the impact of age, presenting features at enrolment, and drug selection. RESULTS: The cohort consisted of 2203 children <15 years of age...
2016: PloS One
https://www.readbyqxmd.com/read/27811066/transmembrane-tnf-%C3%AE-facilitates-hiv-1-infection-of-podocytes-cultured-from-children-with-hiv-associated-nephropathy
#17
Jinliang Li, Jharna R Das, Pingtao Tang, Zhe Han, Jyoti K Jaiswal, Patricio E Ray
Studies have shown that podocytes and renal tubular epithelial cells from patients with HIV-associated nephropathy (HIVAN) express HIV-1 transcripts, suggesting that productive infection of renal epithelial cells precipitates development of HIVAN. However, podocytes and renal tubular epithelial cells do not express CD4 receptors, and it is unclear how these cells become productively infected in vivo We investigated the mechanisms underlying the infection by HIV-1 of podocytes cultured from the urine of children with HIVAN...
November 3, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27809912/frequency-and-env-determinants-of-hiv-1-subtype-c-strains-from-antiretroviral-therapy-naive-subjects-that-display-incomplete-inhibition-by-maraviroc
#18
Katharina Borm, Martin R Jakobsen, Kieran Cashin, Jacqueline K Flynn, Paula Ellenberg, Lars Ostergaard, Benhur Lee, Melissa J Churchill, Michael Roche, Paul R Gorry
BACKGROUND: Entry of human immunodeficiency virus type 1 (HIV-1) into cells involves the interaction of the viral gp120 envelope glycoproteins (Env) with cellular CD4 and a secondary coreceptor, which is typically one of the chemokine receptors CCR5 or CXCR4. CCR5-using (R5) HIV-1 strains that display reduced sensitivity to CCR5 antagonists can use antagonist-bound CCR5 for entry. In this study, we investigated whether naturally occurring gp120 alterations in HIV-1 subtype C (C-HIV) variants exist in antiretroviral therapy (ART)-naïve subjects that may influence their sensitivity to the CCR5 antagonist maraviroc (MVC)...
November 3, 2016: Retrovirology
https://www.readbyqxmd.com/read/27807020/miliary-tuberculosis-in-an-immunocompetent-male-with-a-fatal-outcome
#19
Louise Dunphy, Elizabeth Keating, T Parke
A man aged 33 years, born in Nepal, but resident in the UK for 7 years presented to the emergency department with a 4-day history of general malaise, fever (temperature 38.6°C) and a non-productive cough. His medical history was unremarkable and no high-risk behaviour was identified. Clinical examination confirmed decreased air entry bilaterally with bibasal crackles. He was tachycardic, with a heart rate of 120 bpm. Further investigation with a 12-lead ECG confirmed supraventricular tachycardia (SVT) which was terminated with vagal manoeuvres...
November 2, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27799218/tlr7-agonist-gs-9620-is-a-potent-inhibitor-of-acute-hiv-1-infection-in-human-peripheral-blood-mononuclear-cells
#20
Rujuta A Bam, Derek Hansen, Alivelu Irrinki, Andrew Mulato, Gregg S Jones, Joseph Hesselgesser, Christian R Frey, Tomas Cihlar, Stephen R Yant
GS-9620 is a potent and selective oral Toll-like receptor 7 (TLR7) agonist that directly activates plasmacytoid dendritic cells (pDCs). GS-9620 suppressed hepatitis B virus (HBV) in animal models of chronic infection and transiently activated HIV expression ex vivo in latently-infected peripheral blood mononuclear cells (PBMCs) from virally suppressed patients. Currently, GS-9620 is under clinical evaluation for treating chronic HBV infection and for reducing latent reservoirs in virally-suppressed HIV-infected patients...
October 31, 2016: Antimicrobial Agents and Chemotherapy
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