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HIV viral dynamics

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https://www.readbyqxmd.com/read/29769442/distinct-biomarker-signatures-in-hiv-acute-infection-associate-with-viral-dynamics-and-reservoir-size
#1
Jeffrey E Teigler, Louise Leyre, Nicolas Chomont, Bonnie Slike, Ningbo Jian, Michael A Eller, Nittaya Phanuphak, Eugène Kroon, Suteeraporn Pinyakorn, Leigh Anne Eller, Merlin L Robb, Jintanat Ananworanich, Nelson L Michael, Hendrik Streeck, Shelly J Krebs
Estimating the size of the viral reservoir is critical for HIV cure strategies. Biomarkers in peripheral circulation may give insights into the establishment of the viral reservoir in compartments not easily accessible. We therefore measured systemic levels of 84 soluble biomarkers belonging to a broad array of immune pathways in acute HIV infection in both antiretroviral therapy-naive (ART-naive) individuals as well as individuals who began ART upon early detection of HIV infection. These biomarkers were measured longitudinally during acute and chronic infection and their relationship to viral reservoir establishment and persistence was assessed...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29769349/hiv-1-activation-of-innate-immunity-depends-strongly-on-the-intracellular-level-of-trex1-and-sensing-of-incomplete-reverse-transcription-products
#2
Swati Kumar, James H Morrison, David Dingli, Eric Poeschla
TREX1 has been reported to degrade cytosolic immune-stimulatory DNA, including viral DNA generated during HIV-1 infection, but the dynamic range of its capacity to suppress innate immune stimulation is unknown and its full role in the viral life cycle remains unclear. A main purpose of our study was to determine how the intracellular level of TREX1 affects HIV-1 activation and avoidance of innate immunity. Using stable over-expression and CRISPR-mediated gene disruption, we engineered a range of TREX1 levels in human THP-1 monocytes...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29756455/characterization-of-the-transmitted-virus-in-an-ongoing-hiv-1-epidemic-driven-by-injecting-drug-use
#3
Elena Dukhovlinova, Alexey Masharsky, Aleksandra Vasileva, Alessandro Porrello, Shuntai Zhou, Olga Toussova, Sergei Verevochkin, Ekaterina Akulova, Dmitrij Frishman, David Montefiori, Celia Labranche, Irving Hoffman, William Miller, Myron S Cohen, Andrei Kozlov, Ronald Swanstrom
Understanding features of the HIV-1 transmission process have the potential to inform biological interventions for prevention. We have examined the transmitted virus in a cohort of people who inject drugs and who are at risk of HIV-1 infection through blood contamination when injecting in a group. This study focused on seven newly infected participants in St. Petersburg, Russia, who were in acute or early infection. We used end-point dilution PCR to amplify single viral genomes to assess the complexity of the transmitted virus...
May 14, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29753928/dynamic-changes-of-th1-th2-th17-cytokines-and-human-beta-defensin-2-in-hiv-infected-patients-with-oral-candidiasis-during-the-first-year-of-highly-active-anti-retroviral-therapy
#4
Xiangzhi Yong, Zhenmin Liu, Lanlan Jiang, Renchuan Tao, Wei Liu, Linlin Zhang, Yuanyuan Peng, Xuefang Lin, Yuxiao Huang
OBJECTIVE: To investigate the change of Th1/Th2/Th17 cytokines and human beta defensin 2 (HBD-2) in HIV-infected patients with oral candidiasis (OC) and gather information about OC-specific immunity. DESIGN: During the 1st year of highly active anti-retroviral therapy (HAART), 25 HIV-infected patients were followed up at the baseline, 3rd, 6th, 12th month. At each visit, oral manifestations were examined; oral rinses were collected and cultured for Candida; peripheral venous blood was taken to determine CD4 + T cell counts and HIV RNA viral load (VL); both unstimulated whole saliva and peripheral venous blood were taken to determine cytokine (IL-4, IL-17(A/F), IFN-γ) and HBD-2 levels...
May 3, 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/29743354/inhibitory-effects-of-hiv-2-vpx-on-replication-of-hiv-1
#5
Mohamed Mahdi, Zsófia Szojka, János András Mótyán, József Tőzsér
The human immunodeficiency viruses type 1 and 2 share a striking genomic resemblance, however, variability in the genetic sequence accounts for the presence of unique accessory genes; such as viral protein x ( vpx ) in HIV-2. Dual infection with both viruses has long been described in the literature, yet the molecular mechanism of how dually infected patients tend to do better than those who are mono-infected with HIV-1 has not yet been explored. We hypothesized that in addition to extracellular mechanisms, an HIV-2 accessory gene is the culprit, and interference at viral accessory/regulatory protein level is perhaps responsible for the attenuated pathogenicity of HIV-1 observed in dually infected patients...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29741638/distribution-of-hiv-rna-in-csf-and-blood-is-linked-to-cd4-cd8-ratio-during-acute-hiv
#6
Phillip Chan, Payal Patel, Joanna Hellmuth, Donn J Colby, Eugène Kroon, Carlo Sacdalan, Suteeraporn Pinyakorn, Linda Jagodzinski, Shelly Krebs, Jintanat Ananworanich, Victor Valcour, Serena Spudich
Background: HIV RNA levels in the plasma and cerebrospinal fluid (CSF) are correlated in chronic HIV infection but their dynamics have not been characterized during acute infection. Methods: This study analyzed predictors of CSF HIV RNA and relative degree of CNS viral transmigration expressed as plasma minus CSF HIV log10 RNA (PCratio) during untreated acute HIV infection. CSF immune markers were compared between groups with different PCratio. Results: 117 mostly male (97%) participants in the RV254 cohort in Bangkok, Thailand, had median age 28 years and an estimated median 18 days duration of infection; forty-three (37%) were Fiebig stages I/II...
May 7, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29733983/evolutionary-dynamics-of-hepatitis-c-virus-in-a-chronic-hiv-co-infected-patient-and-its-correlation-with-the-immune-status
#7
Andrés Carlos Alberto Culasso, María Cecilia Monzani, Patricia Baré, Rodolfo Hector Campos
The HCV evolutionary dynamics play a key role in the infection onset, maintenance of chronicity, pathogenicity, and drug resistance variants fixation, and are thought to be one of the main caveats in the development of an effective vaccine. Previous studies in HCV/HIV co-infected patients suggest that a decline in the immune status is related with increases in the HCV intra-host genetic diversity. However, these findings are based on single point sequence diversity measures or coalescence analyses in several virus-host interactions...
May 4, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29725327/lymph-node-cellular-and-viral-dynamics-in-natural-hosts-and-impact-for-hiv-cure-strategies
#8
REVIEW
Nicolas Huot, Steven E Bosinger, Mirko Paiardini, R Keith Reeves, Michaela Müller-Trutwin
Combined antiretroviral therapies (cARTs) efficiently control HIV replication leading to undetectable viremia and drastic increases in lifespan of people living with HIV. However, cART does not cure HIV infection as virus persists in cellular and anatomical reservoirs, from which the virus generally rebounds soon after cART cessation. One major anatomical reservoir are lymph node (LN) follicles, where HIV persists through replication in follicular helper T cells and is also trapped by follicular dendritic cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29705491/structural-discordance-in-hiv-1-vpu-from-brain-isolate-alarms-amyloid-fibril-forming-behavior-a-computational-perspective
#9
Sneha Patil, Pritam Kumar Panda, Fatemeh Gharemirshamlu Rahimi, Kourosh Bamdad, Seetharaman Balaji
HIV-1 being the most widespread type worldwide accounts for almost 95% of all infections including HIV associated dementia (HAD) that triggers neurological dysfunction and neurodegeneration in patients. The common features associated with HAD and other neurodegenerative diseases are accumulation of amyloid plaques, neuronal loss and deterioration of cognitive abilities, amongst which amyloid fibrillation is considered to be a hallmark. The success of effective therapeutics lies in the understanding of mechanisms leading to neurotoxicity...
April 26, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29684141/insights-about-minority-hiv-1-strains-in-transmitted-drug-resistance-mutation-dynamics-and-disease-progression
#10
Ana Rachel Leda, James Hunter, Ursula Castro Oliveira, Inacio Junqueira Azevedo, Maria Cecilia Araripe Sucupira, Ricardo Sobhie Diaz
Objectives: The presence of minority transmitted drug resistance mutations was assessed using ultra-deep sequencing and correlated with disease progression among recently HIV-1-infected individuals from Brazil. Methods: Samples at baseline during recent infection and 1 year after the establishment of the infection were analysed. Viral RNA and proviral DNA from 25 individuals were subjected to ultra-deep sequencing of the reverse transcriptase and protease regions of HIV-1...
April 19, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29683993/impact-of-improved-hiv-care-and-treatment-on-prep-effectivenesss-in-the-united-states-2016-2020
#11
Nidhi Khurana, Emine Yaylali, Paul G Farnham, Katherine A Hicks, Benjamin T Allaire, Evin Jacobson, Stephanie L Sansom
BACKGROUND: The effect of improving diagnosis, care, and treatment of persons living with HIV (PLWH) on PrEP effectiveness in the United States has not be well established. METHODS: We used a dynamic, compartmental model that simulates the sexually active US population. We investigated the change in cumulative HIV incidence from 2016 to 2020 for three HIV care continuum levels, and the marginal benefit of PrEP compared with each. We also explored the marginal benefit of PrEP for individual risk groups, and as PrEP adherence, coverage and dropout rates varied...
April 20, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29682300/latent-hiv-dynamics-and-implications-for-sustained-viral-suppression-in-the-absence-of-antiretroviral-therapy
#12
EDITORIAL
John M Murray
Objectives: The interaction between HIV and the immune system gives rise to a complex dynamical system. We therefore investigate whether delayed viral rebound after antiretroviral therapy (ART) interruption (ATI) may be due to an individual's viral-immune state being in a region of relative stability, and if so, how this can be extended. Methods: Using a mathematical model duplicating plasma viral levels, HIV DNA and immune homeostatic dynamics for individuals on ART commenced at either primary (PHI) or chronic (CHI) HIV infection, we investigate whether latent reservoir reductions and perturbations in other infected and uninfected memory CD4+ T cell subsets can delay viral rebound...
April 1, 2018: Journal of Virus Eradication
https://www.readbyqxmd.com/read/29677208/modeling-the-dynamics-and-kinetics-of-hiv-1-gag-during-viral-assembly
#13
Michael D Tomasini, Daniel S Johnson, Joshua S Mincer, Sanford M Simon
We report a computational model for the assembly of HIV-1 Gag into immature viral particles at the plasma membrane. To reproduce experimental structural and kinetic properties of assembly, a process occurring on the order of minutes, a coarse-grained representation consisting of a single particle per Gag molecule is developed. The model uses information relating the functional interfaces implicated in Gag assembly, results from cryo electron-tomography, and biophysical measurements from fluorescence microscopy, such as the dynamics of Gag assembly at single virions...
2018: PloS One
https://www.readbyqxmd.com/read/29658302/molecular-epidemiology-of-hiv-1-virus-in-puerto-rico-novel-cases-of-hiv-1-subtype-c-d-and-crf-24bg
#14
Pablo Lopez, Omayra De Jesus, Yasuhiro Yamamura, Nayra Rodriguez, Andrea Arias, Raphael Sanchez, Yadira Rodriguez, Vivian Tamayo-Agrait, Wilfredo Cuevas, Vanessa Rivera-Amill
Human immunodeficiency virus-1 (HIV-1) subtype B virus is the most prevalent subtype in Puerto Rico (PR), accounting for about 90% of infection in the island. Recently, other subtypes and circulating recombinant forms (CRF) including F (12_BF), A (01_BF), and CRF-39 BF-like have been identified. The purpose of this study is to assess the distribution of drug resistance mutations and subtypes in PR. A total of 846 nucleotide sequences from the period comprising 2013 through 2017 were obtained from our "HIV Genotyping" test file...
April 15, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29643844/emerging-roles-of-n-6-methyladenosine-on-hiv-1-rna-metabolism-and-viral-replication
#15
REVIEW
Sebastián Riquelme-Barrios, Camila Pereira-Montecinos, Fernando Valiente-Echeverría, Ricardo Soto-Rifo
N6 -methyladenosine (m6 A) is the most abundant internal modification present in Eukaryotic mRNA. The functions of this chemical modification are mediated by m6 A-binding proteins (m6 A readers) and regulated by methyltransferases (m6 A writers) and demethylases (m6 A erasers), which together are proposed to be responsible of a new layer of post-transcriptional control of gene expression. Despite the presence of m6 A in a retroviral genome was reported more than 40 years ago, the recent development of sequencing-based technologies allowing the mapping of m6 A in a transcriptome-wide manner made it possible to identify the topology and dynamics of m6 A during replication of HIV-1 as well as other viruses...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29643246/the-dynamics-of-siv-2-ltr-circles-in-the-presence-and-absence-of-cd8-cells
#16
Benjamin B Policicchio, Erwing Fabian Cardozo, Paola Sette, Cuiling Xu, George Haret-Richter, Tammy Dunsmore, Cristian Apetrei, Ivona Pandrea, Ruy M Ribeiro
CD8+ cells play a key role in HIV/SIV infection, but their specific mechanism(s) of action in controlling the virus are unclear. 2-LTR circles are extrachromosomal products generated upon failed integration of HIV/SIV. To understand the specific effects of CD8+ cells on infected cells, we analyzed the dynamics of 2-LTR circles in SIVmac251-infected rhesus macaques (RM) treated with an integrase inhibitor (INT). Twenty RMs underwent CD8+ cell depletion, received RAL monotherapy or a combination of both. Blood, lymph nodes (LNs) and gut biopsies were routinely sampled...
April 11, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29625416/molecular-dynamics-and-ligand-docking-of-a-hinge-region-variant-of-south-african-hiv-1-subtype-c-protease
#17
Jake Zondagh, Vijayakumar Balakrishnan, Ikechukwu Achilonu, Heini W Dirr, Yasien Sayed
HIV-1 protease is an important antiretroviral drug target due to its key role in viral maturation. Computational models have been successfully used in the past to understand the dynamics of HIV-1 protease variants. We performed molecular dynamics simulations and induced fit docking on a wild-type South African HIV-1 subtype C protease and an N37T↑V hinge region variant. The simulations were initiated in a cubic cell universe and run in explicit solvent, with the wild-type and variant proteases in the fully closed conformation and under periodic boundary conditions...
March 27, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29620933/dynamics-of-lymphocyte-reconstitution-after-hematopoietic-transplantation-during-chronic-lymphocytic-choriomeningitis-virus-infection
#18
Mitra Bhattacharyya, Pablo Penaloza-MacMaster
Bone marrow transplantation is a treatment for various cancers and genetic diseases, and the only case of a cured HIV infection involved the use of this clinical procedure, highlighting the potential use of this therapy for curing many chronic diseases. However, little is known about how chronic viral infection influences lymphocyte reconstitution after bone marrow transplantation. To address this, we infected mice with chronic lymphocytic choriomeningitis virus, and performed bone marrow transplantation to assess lymphocyte reconstitution...
May 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29614069/prediction-of-extended-high-viremia-among-newly-hiv-1-infected-persons-in-sub-saharan-africa
#19
Kimberly A Powers, Matthew A Price, Etienne Karita, Anatoli Kamali, William Kilembe, Susan Allen, Eric Hunter, Linda-Gail Bekker, Shabir Lakhi, Mubiana Inambao, Omu Anzala, Mary H Latka, Patricia E Fast, Jill Gilmour, Eduard J Sanders
OBJECTIVE: Prompt identification of newly HIV-infected persons, particularly those who are most at risk of extended high viremia (EHV), allows important clinical and transmission prevention benefits. We sought to determine whether EHV could be predicted during early HIV infection (EHI) from clinical, demographic, and laboratory indicators in a large HIV-1 incidence study in Africa. DESIGN: Adults acquiring HIV-1 infection were enrolled in an EHI study assessing acute retroviral syndrome (ARS) symptoms and viral dynamics...
2018: PloS One
https://www.readbyqxmd.com/read/29611111/caspase-1-associated-immune-activation-in-an-accelerated-siv-infected-rhesus-macaque-model
#20
Alison C Kearns, Jake A Robinson, Masoud Shekarabi, Fengming Liu, Xuebin Qin, Tricia H Burdo
In the antiretroviral therapy (ART) era, chronic HIV infection is primarily associated with chronic inflammation driving comorbidities such as cardiovascular disease and neurocognitive impairment. Caspase-1 activation in leukocytes has been documented in HIV infection; however, whether caspase-1 activation and the downstream pro-inflammatory cytokines interleukin-1beta (IL-1β) and interleukin-18 (IL-18) contribute to chronic inflammation in HIV comorbidities remains undetermined. The relationship between the caspase-1 cascade and persistent inflammation in HIV has not been investigated...
April 2, 2018: Journal of Neurovirology
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