Identification of HIV-1 genetic associations with coreceptor usage and neurocognitive impairment

2021 ◽  
Author(s):  
Gregory C. Antell
Keyword(s):  
Neurocognitive Impairment ◽  
Coreceptor Usage ◽  
Genetic Associations ◽  
Hiv 1

scholarly journals Genome-Wide Association Study of Human Immunodeficiency Virus (HIV)-1 Coreceptor Usage in Treatment-Naive Patients from An AIDS Clinical Trials Group Study

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Timothy J. Henrich ◽  
Paul J. McLaren ◽  
Suhas S. P. Rao ◽  
Nina H. Lin ◽  
Emily Hanhauser ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Coreceptor Usage ◽  
Genome Wide ◽  
Immunodeficiency Virus ◽  
Treatment Naïve ◽  
Host Genetic ◽  
Aids Clinical Trials ◽  
Hiv 1

Abstract Objectives.  We conducted a genome-wide association study to explore whether common host genetic variants (>5% frequency) were associated with presence of virus able to use CXCR4 for entry. Methods.  Phenotypic determination of human immunodeficiency virus (HIV)-1 coreceptor usage was performed on pretreatment plasma HIV-1 samples from treatment-naive participants in AIDS Clinical Trials Group A5095, a study of initial antiretroviral regimens. Associations between genome-wide single-nucleotide polymorphisms (SNPs), CCR5 Δ32 genotype, and human leukocyte antigen (HLA) class I alleles and viral coreceptor usage were explored. Results.  Viral phenotypes were obtained from 593 patients with available genome-wide SNP data. Forty-four percent of subjects had virus capable of using CXCR4 for entry as determined by phenotyping. Overall, no associations, including those between polymorphisms in genes encoding viral coreceptors and their promoter regions or in HLA genes previously associated with HIV-1 disease progression, passed the statistical threshold for genome-wide significance (P < 5.0 × 10−8) in any comparison. However, the presence of viruses able to use CXCR4 for entry was marginally associated with the CCR5 Δ32 genotype in the nongenome-wide analysis. Conclusions.  No human genetic variants were significantly associated with virus able to use CXCR4 for entry at the genome-wide level. Although the sample size had limited power to definitively exclude genetic associations, these results suggest that host genetic factors, including those that influence coreceptor expression or the immune pressures leading to viral envelope diversity, are either rare or have only modest effects in determining HIV-1 coreceptor usage.

scholarly journals Coreceptor Usage, Diversity, and Divergence in Drug-Naive and Drug-Exposed Individuals from Malawi, Infected with HIV-1 Subtype C for More Than 20 Years

2014 ◽  
Vol 30 (10) ◽  
pp. 975-983 ◽  
Author(s):  
Ishla Seager ◽  
Simon A. Travers ◽  
Michael D. Leeson ◽  
Amelia C. Crampin ◽  
Neil French ◽  
...  
Keyword(s):  
Coreceptor Usage ◽  
Subtype C ◽  
Drug Naïve ◽  
Hiv 1

scholarly journals HIV-1 Dynamics and Coreceptor Usage in Maraviroc-Treated Patients with Ongoing Replication

2012 ◽  
Vol 57 (2) ◽  
pp. 930-935 ◽  
Author(s):  
P. Recordon-Pinson ◽  
S. Raymond ◽  
P. Bellecave ◽  
A. G. Marcelin ◽  
C. Soulie ◽  
...  
Keyword(s):  
Coreceptor Usage ◽  
Hiv 1

scholarly journals Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation

2005 ◽  
Vol 86 (12) ◽  
pp. 3385-3396 ◽  
Author(s):  
Yu Shi ◽  
Eleonor Brandin ◽  
Elzbieta Vincic ◽  
Marianne Jansson ◽  
Anders Blaxhult ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Neutralizing Antibodies ◽  
Coreceptor Usage ◽  
Glycosylation Pattern ◽  
Immunodeficiency Virus ◽  
Envelope Sequence ◽  
Hiv 1

To investigate why human immunodeficiency virus type 2 (HIV-2) is less virulent than HIV-1, the evolution of coreceptor usage, autologous neutralization, envelope sequence and glycosylation was studied in sequentially obtained virus isolates and sera from four HIV-2-infected individuals. Neutralization of primary HIV-2 isolates was tested by a cell line-based assay and IgG purified from patients' sera. Significant autologous neutralization was observed for the majority (39 of 54) of the HIV-2 serum–virus combinations tested, indicating that neutralization escape is rare in HIV-2 infection. Furthermore, sera from 18 HIV-2 patients displayed extensive heterologous cross-neutralization when tested against a panel of six primary HIV-2 isolates. This indicates that HIV-2 is intrinsically more sensitive to antibody neutralization than HIV-1. In line with earlier reports, HIV-2 isolates could use several alternative receptors in addition to the major coreceptors CCR5 and CXCR4. Intrapatient evolution from CCR5 use to CXCR4 use was documented for the first time. Furthermore, CXCR4 use was linked to the immunological status of the patients. Thus, all CXCR4-using isolates, except one, were obtained from patients with CD4 counts below 200 cells μl−1. Sequence analysis revealed an association between coreceptor usage and charge of the V3 loop of the HIV-2 envelope, as well as an association between the rate of disease progression and the glycosylation pattern of the envelope protein. Furthermore, HIV-2 isolates had fewer glycosylation sites in the V3 domain than HIV-1 (two to three versus four to five). It is proposed here that HIV-2 has a more open and accessible V3 domain than HIV-1, due to differences in glycan packing, and that this may explain its broader coreceptor usage and greater sensitivity to neutralizing antibodies.

HIV-1 coreceptor usage and CXCR4-specific viral load predict clinical disease progression during combination antiretroviral therapy

AIDS ◽  
2008 ◽  
Vol 22 (4) ◽  
pp. 469-479 ◽  
Author(s):  
Barbara Weiser ◽  
Sean Philpott ◽  
Thomas Klimkait ◽  
Harold Burger ◽  
Christina Kitchen ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Disease Progression ◽  
Clinical Disease ◽  
Coreceptor Usage ◽  
Combination Antiretroviral Therapy ◽  
Hiv 1 ◽  
Clinical Disease Progression

scholarly journals Simian-Human Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Subtype-E Envelope Gene: Persistent Infection, CD4+ T-Cell Depletion, and Mucosal Membrane Transmission in Macaques

2000 ◽  
Vol 74 (17) ◽  
pp. 7851-7860 ◽  
Author(s):  
Sunee Himathongkham ◽  
Nancy S. Halpin ◽  
Jinling Li ◽  
Michael W. Stout ◽  
Christopher J. Miller ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Nonhuman Primate ◽  
Coreceptor Usage ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Recombinant Clone ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The envelope (env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) determines several viral properties (e.g., coreceptor usage, cell tropism, and cytopathicity) and is a major target of antiviral immune responses. Most investigations on env have been conducted on subtype-B viral strains, prevalent in North America and Europe. Our study aimed to analyze env genes of subtype-E viral strains, prevalent in Asia and Africa, with a nonhuman primate model for lentivirus infection and AIDS. To this end, we constructed a simian immunodeficiency virus/HIV-1 subtype-E (SHIV) recombinant clone by replacing the env ectodomain of the SHIV-33 clone with theenv ectodomain from the subtype-E strain HIV-1CAR402, which was isolated from an individual in the Central African Republic. Virus from this recombinant clone, designated SHIV-E-CAR, replicated efficiently in macaque peripheral blood mononuclear cells. Accordingly, juvenile macaques were inoculated with cell-free SHIV-E-CAR by the intravenous or intravaginal route; virus replicated in these animals but did not produce hematological abnormalities. In an attempt to elicit the pathogenic potential of the recombinant clone, we serially passaged this viral clone via transfusion of blood and bone marrow through juvenile macaques to produce SHIV-E-P4 (fourth-passage virus). The serially passaged virus established productive infection and CD4+ T-cell depletion in juvenile macaques inoculated by either the intravenous or the intravaginal route. Determination of the coreceptor usage of SHIV-E-CAR and serially passaged SHIV-E-P4 indicated that both of these viruses utilized CXCR4 as a coreceptor. In summary, the serially passaged SHIV subtype-E chimeric virus will be important for studies aimed at developing a nonhuman primate model for analyzing the functions of subtype-E env genes in viral transmission and pathogenesis and for vaccine challenge experiments with macaques immunized with HIV-1 env antigens.

High Rates of Asymptomatic Neurocognitive Impairment in Vertically Acquired HIV-1–Infected Adolescents Surviving to Adulthood

2010 ◽  
Vol 55 (1) ◽  
pp. 134-136 ◽  
Author(s):  
Yasotharan Paramesparan ◽  
Lucy J Garvey ◽  
Jane Ashby ◽  
Caroline J Foster ◽  
Sarah Fidler ◽  
...  
Keyword(s):  
Neurocognitive Impairment ◽  
Asymptomatic Neurocognitive Impairment ◽  
Hiv 1
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