scholarly journals Host Genetic and Viral Determinants of HIV-1 RNA Set Point among HIV-1 Seroconverters from Sub-Saharan Africa

2014 ◽  
Vol 89 (4) ◽  
pp. 2104-2111 ◽  
Author(s):  
Romel D. Mackelprang ◽  
Mary Carrington ◽  
Katherine K. Thomas ◽  
James P. Hughes ◽  
Jared M. Baeten ◽  
...  
Keyword(s):  
Immune Responses ◽  
Human Leukocyte ◽  
Sub Saharan Africa ◽  
Host Responses ◽  
Adaptive Immune Responses ◽  
Hla Alleles ◽  
Set Point ◽  
Transmission Potential ◽  
Adaptive Immune ◽  
Hiv 1

ABSTRACTWe quantified the collective impact of source partner HIV-1 RNA levels, human leukocyte antigen (HLA) alleles, and innate responses through Toll-like receptor (TLR) alleles on the HIV-1 set point. Data came from HIV-1 seroconverters in African HIV-1 serodiscordant couple cohorts. Linear regression was used to determine associations with set point andR2to estimate variation explained by covariates. The strongest predictors of set point were HLA alleles (B*53:01, B*14:01, and B*27:03) and plasma HIV-1 levels of the transmitting partner, which explained 13% and 10% of variation in set point, respectively. HLA-A concordance between partners and TLR polymorphisms (TLR2rs3804100 andTLR7rs179012) also were associated with set point, explaining 6% and 5% of the variation, respectively. Overall, these factors and genital factors of the transmitter (i.e., male circumcision, bacterial vaginosis, and use of acyclovir) explained 46% of variation in set point. We found that both innate and adaptive immune responses, together with plasma HIV-1 levels of the transmitting partner, explain almost half of the variation in viral load set point.IMPORTANCEAfter HIV-1 infection, uncontrolled virus replication leads to a rapid increase in HIV-1 concentrations. Once host immune responses develop, however, HIV-1 levels reach a peak and subsequently decline until they reach a stable level that may persist for years. This stable HIV-1 set point represents an equilibrium between the virus and host responses and is predictive of later disease progression and transmission potential. Understanding how host and virus factors interact to determine HIV-1 set point may elucidate novel mechanisms or biological pathways for treating HIV-1 infection. We identified host and virus factors that predict HIV-1 set point in people who recently acquired HIV-1, finding that both innate and adaptive immune responses, along with factors that likely influence HIV-1 virulence and inoculum, explain ∼46% of the variation in HIV-1 set point.

scholarly journals Identification of risk and protective human leukocyte antigens in COVID-19 using genotyping and structural modeling

2021 ◽  
Author(s):  
Yiran Shen ◽  
David Ostrov ◽  
Santosh Rananaware ◽  
Piyush K Jain ◽  
Cuong Nguyen
Keyword(s):  
Immune Deficiency ◽  
Immune Responses ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Leukocyte Antigens ◽  
Disease Mechanisms ◽  
Unknown Risk ◽  
Increased Risk

COVID-19 is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The severity of COVID-19 is highly variable and related to known (e.g., age, obesity, immune deficiency) and unknown risk factors. Since innate and adaptive immune responses are elicited in COVID-19 patients, we genotyped 94 Florida patients with confirmed COVID-19 and 89 healthy controls. We identified an HLA gene, HLA-DPA1, in which specific alleles were associated with the risk of SARS-CoV-2 positivity and COVID-19 disease. HLA-DPA1*01:03 was associated with reduced incidence of SARS-CoV-2 positivity, whereas HLA-DPA1*03:01 was associated with increased risk of SARS-CoV-2 positivity. These data suggest a model in which COVID-19 severity is influenced by immunodominant peptides derived from SARS-CoV-2 preferentially presented by specific HLA-DP molecules to either protective (for asymptomatic COVID-19) or pathogenic T cells (in severe COVID-19). Although this study is limited to comparing SARS-CoV-2 positive and negative subjects, these data suggest that HLA typing of COVID-19 patients stratified for disease severity may be informative for identifying biomarkers and disease mechanisms in high-risk individuals

scholarly journals Human Leukocyte Antigen Genotypes in the Genetic Control of Adaptive Immune Responses to Smallpox Vaccine

2011 ◽  
Vol 203 (11) ◽  
pp. 1546-1555 ◽  
Author(s):  
Inna G. Ovsyannikova ◽  
Robert A. Vierkant ◽  
V. Shane Pankratz ◽  
Robert M. Jacobson ◽  
Gregory A. Poland
Keyword(s):  
Immune Responses ◽  
Human Leukocyte Antigen ◽  
Genetic Control ◽  
Human Leukocyte ◽  
Smallpox Vaccine ◽  
Adaptive Immune Responses ◽  
Leukocyte Antigen ◽  
Adaptive Immune

scholarly journals HistoplasmaVirulence and Host Responses

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Mircea Radu Mihu ◽  
Joshua Daniel Nosanchuk
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Respiratory Disease ◽  
Histoplasma Capsulatum ◽  
Current Knowledge ◽  
Complex Interaction ◽  
Host Responses ◽  
Adaptive Immune Responses ◽  
Disease Extent ◽  
Adaptive Immune

Histoplasma capsulatumis the most prevalent cause of fungal respiratory disease. The disease extent and outcomes are the result of the complex interaction between the pathogen and a host's immune system. The focus of our paper consists in presenting the current knowledge regarding the multiple facets of the dynamic host-pathogen relationship in the context of the virulence arsenal displayed by the fungus and the innate and adaptive immune responses of the host.

scholarly journals Endotoxemia Is Associated with Altered Innate and Adaptive Immune Responses in Untreated HIV-1 Infected Individuals

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e21275 ◽  
Author(s):  
Anne Roslev Bukh ◽  
Jesper Melchjorsen ◽  
Rasmus Offersen ◽  
Jens Magnus Bernth Jensen ◽  
Lars Toft ◽  
...  
Keyword(s):  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Hiv 1

scholarly journals SAMHD1 Limits HIV-1 Antigen Presentation by Monocyte-Derived Dendritic Cells

2015 ◽  
Vol 89 (14) ◽  
pp. 6994-7006 ◽  
Author(s):  
Diana Ayinde ◽  
Timothée Bruel ◽  
Sylvain Cardinaud ◽  
Françoise Porrot ◽  
Julia G. Prado ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antigen Presentation ◽  
Cytotoxic T Lymphocytes ◽  
Viral Proteins ◽  
Productive Infection ◽  
Restriction Factors ◽  
Adaptive Immune Responses ◽  
Mhc I ◽  
Adaptive Immune ◽  
Hiv 1

ABSTRACTMonocyte-derived dendritic cells (MDDC) stimulate CD8+cytotoxic T lymphocytes (CTL) by presenting endogenous and exogenous viral peptides via major histocompatibility complex class I (MHC-I) molecules. MDDC are poorly susceptible to HIV-1, in part due to the presence of SAMHD1, a cellular enzyme that depletes intracellular deoxynucleoside triphosphates (dNTPs) and degrades viral RNA. Vpx, an HIV-2/SIVsm protein absent from HIV-1, antagonizes SAMHD1 by inducing its degradation. The impact of SAMHD1 on the adaptive cellular immune response remains poorly characterized. Here, we asked whether SAMHD1 modulates MHC-I-restricted HIV-1 antigen presentation. Untreated MDDC or MDDC pretreated with Vpx were exposed to HIV-1, and antigen presentation was examined by monitoring the activation of an HIV-1 Gag-specific CTL clone. SAMHD1 depletion strongly enhanced productive infection of MDDC as well as endogenous HIV-1 antigen presentation. Time-lapse microscopy analysis demonstrated that in the absence of SAMHD1, the CTL rapidly killed infected MDDC. We also report that various transmitted/founder (T/F) HIV-1 strains poorly infected MDDC and, as a consequence, did not stimulate CTL. Vesicular stomatitis virus glycoprotein (VSV-G) pseudotyping of T/F alleviated a block in viral entry and induced antigen presentation only in the absence of SAMHD1. Furthermore, by using another CTL clone that mostly recognizes incoming HIV-1 antigens, we demonstrate that SAMHD1 does not influence exogenous viral antigen presentation. Altogether, our results demonstrate that the antiviral activity of SAMHD1 impacts antigen presentation by DC, highlighting the link that exists between restriction factors and adaptive immune responses.IMPORTANCEUpon viral infection, DC may present antigens derived from incoming viral material in the absence of productive infection of DC or from newly synthesized viral proteins. In the case of HIV, productive infection of DC is blocked at an early postentry step. This is due to the presence of SAMHD1, a cellular enzyme that depletes intracellular levels of dNTPs and inhibits viral reverse transcription. We show that the depletion of SAMHD1 in DCs strongly stimulates the presentation of viral antigens derived from newly produced viral proteins, leading to the activation of HIV-1-specific cytotoxic T lymphocytes (CTL). We further show in real time that the enhanced activation of CTL leads to killing of infected DCs. Our results indicate that the antiviral activity of SAMHD1 not only impacts HIV replication but also impacts antigen presentation by DC. They highlight the link that exists between restriction factors and adaptive immune responses.

scholarly journals Innate and Adaptive Immune Responses Both Contribute to Pathological CD4 T Cell Activation in HIV-1 Infected Ugandans

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18779 ◽  
Author(s):  
Michael A. Eller ◽  
Kim G. Blom ◽  
Veronica D. Gonzalez ◽  
Leigh Anne Eller ◽  
Prossy Naluyima ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Hiv 1

scholarly journals Restriction by SAMHD1 Limits cGAS/STING-Dependent Innate and Adaptive Immune Responses to HIV-1

Cell Reports ◽  
2016 ◽  
Vol 16 (6) ◽  
pp. 1492-1501 ◽  
Author(s):  
Jonathan Maelfait ◽  
Anne Bridgeman ◽  
Adel Benlahrech ◽  
Chiara Cursi ◽  
Jan Rehwinkel
Keyword(s):  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Hiv 1

scholarly journals HIV and SIV in Body Fluids: From Breast Milk to the Genitourinary Tract

2019 ◽  
Vol 15 (1) ◽  
pp. 139-152
Author(s):  
Kattayoun Kordy ◽  
Nicole H. Tobin ◽  
Grace M. Aldrovandi
Keyword(s):  
Antiretroviral Therapy ◽  
Breast Milk ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Hiv Rna ◽  
Adaptive Immune ◽  
Hiv Dna ◽  
Current State ◽  
Repetitive Exposure ◽  
Hiv 1

HIV-1 is present in many secretions including oral, intestinal, genital, and breast milk. However, most people exposed to HIV-1 within these mucosal compartments do not become infected despite often frequent and repetitive exposure over prolonged periods of time. In this review, we discuss what is known about the levels of cell-free HIV RNA, cell-associated HIV DNA and cellassociated HIV RNA in external secretions. Levels of virus are usually lower than contemporaneously obtained blood, increased in settings of inflammation and infection, and decreased in response to antiretroviral therapy. Additionally, each mucosal compartment has unique innate and adaptive immune responses that affect the composition and presence of HIV-1 within each external secretion. We discuss the current state of knowledge about the types and amounts of virus present in the various excretions, touch on innate and adaptive immune responses as they affect viral levels, and highlight important areas for further study.

Potent adaptive immune responses induced against HIV-1 gp140 and influenza virus HA by a polyanionic carbomer

Vaccine ◽  
2010 ◽  
Vol 28 (13) ◽  
pp. 2482-2489 ◽  
Author(s):  
George Krashias ◽  
Anna-Katharina Simon ◽  
Frank Wegmann ◽  
Wai-Ling Kok ◽  
Ling-Pei Ho ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Hiv 1
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