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The rapid CD4?+?T-lymphocyte decline and human immunodeficiency virus progression in females compared to males.

ABSTRACT: CD4?+?T-lymphocyte counts are used to assess CD4?+?decline and the stage of human immunodeficiency virus (HIV) progression in HIV-infected patients. Clinical observation suggests that HIV progress more rapid in females than males. Of the original 5000 HIV-infected population of Western New York HIV/AIDS, Referral Center at Erie County Medical Center (ECMC), 1422 participated in the cohort study. We identified 333 HIV-infected patients with CD4?+?T-cell-counts???500/µ?, among them 178 met the inclusion criteria for the 10-year study. Females had higher mode (600 vs. 540) and mean (741.9 vs. 712.2) CD4?+?counts than males at baseline. However, CD4?+?declined faster among females in a shorter time than males (234.5 vs. 158.6, P?

SUBMITTER: Parsa N

PROVIDER: S-EPMC7544823 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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The rapid CD4 + T-lymphocyte decline and human immunodeficiency virus progression in females compared to males.

Parsa Nader N Zaheri Pari Mahlagha PM Hewitt Ross G RG Karimi Akhormeh Ali A Taravatmanesh Samira S Wallin Lisa L

Scientific reports 20201008 1

CD4 + T-lymphocyte counts are used to assess CD4 + decline and the stage of human immunodeficiency virus (HIV) progression in HIV-infected patients. Clinical observation suggests that HIV progress more rapid in females than males. Of the original 5000 HIV-infected population of Western New York HIV/AIDS, Referral Center at Erie County Medical Center (ECMC), 1422 participated in the cohort study. We identified 333 HIV-infected patients with CD4 + T-cell-counts ≥ 500/µƖ, among them 178 met the inc ...[more]

PMID: 33033335

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Project description:BackgroundThe identification of biomarkers for early detection of Alzheimer's disease (AD) is critical to the development of therapies and interventions targeted at symptom management and tracking the pathophysiology of disease. The endorsement of subjective cognitive decline (SCD) has emerged as a potential indicator of early change in cognitive status that may be predictive of future impairment at a time when measurable declines in neuropsychological performance cannot be detected. While there are numerous findings revealing sex differences in the prevalence of AD, there is a paucity of research examining sex differences in SCD. Therefore, the goal of this project was to determine if the relationship between the endorsement of SCD and future cognitive changes differ as a function of biological sex.MethodsA sample of 3019 male and female healthy older adults (2188 without SCD, 831 with SCD), with a mean follow-up time of 5.7 years, were included from the Rush Alzheimer's Disease Center Research Sharing Hub. Linear regressions were performed to determine group differences in baseline cognitive scores, while linear mixed-effects models were completed to determine group differences in the rate of cognitive change over time.ResultsIndividuals endorsing SCD had significantly lower baseline cognitive scores and increased rates of decline in all cognitive domains compared to those without SCD. Males exhibited significantly lower scores in baseline performance in global cognition, episodic memory, and perceptual speed regardless of SCD classification. Females with SCD were found to decline at significantly faster rates than both males with SCD and males and females without SCD in all cognitive domains over a maximum 15-year follow-up period.ConclusionsSCD is related to lower baseline cognitive performance and faster cognitive decline compared to those who do not endorse SCD. Females with SCD have the fastest rate of decline suggesting that SCD may be more predictive of future decline in females than in males. Targeted assessments of SCD may allow for the identification of individuals for inclusion in intervention trials, and other research studies, aiming to attenuate casual disease processes, which may ultimately aid in the mitigation of sex disparities in AD.

Project description:UnlabelledCD4 tropism is conserved among all primate lentiviruses and likely contributes to viral pathogenesis by targeting cells that are critical for adaptive antiviral immune responses. Although CD4-independent variants of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) have been described that can utilize the coreceptor CCR5 or CXCR4 in the absence of CD4, these viruses typically retain their CD4 binding sites and still can interact with CD4. We describe the derivation of a novel CD4-independent variant of pathogenic SIVmac239, termed iMac239, that was used to derive an infectious R5-tropic SIV lacking a CD4 binding site. Of the seven mutations that differentiate iMac239 from wild-type SIVmac239, a single change (D178G) in the V1/V2 region was sufficient to confer CD4 independence in cell-cell fusion assays, although other mutations were required for replication competence. Like other CD4-independent viruses, iMac239 was highly neutralization sensitive, although mutations were identified that could confer CD4-independent infection without increasing its neutralization sensitivity. Strikingly, iMac239 retained the ability to replicate in cell lines and primary cells even when its CD4 binding site had been ablated by deletion of a highly conserved aspartic acid at position 385, which, for HIV-1, plays a critical role in CD4 binding. iMac239, with and without the D385 deletion, exhibited an expanded host range in primary rhesus peripheral blood mononuclear cells that included CCR5(+) CD8(+) T cells. As the first non-CD4-tropic SIV, iMac239-ΔD385 will afford the opportunity to directly assess the in vivo role of CD4 targeting on pathogenesis and host immune responses.ImportanceCD4 tropism is an invariant feature of primate lentiviruses and likely plays a key role in pathogenesis by focusing viral infection onto cells that mediate adaptive immune responses and in protecting virions attached to cells from neutralizing antibodies. Although CD4-independent viruses are well described for HIV and SIV, these viruses characteristically retain their CD4 binding site and can engage CD4 if available. We derived a novel CD4-independent, CCR5-tropic variant of the pathogenic molecular clone SIVmac239, termed iMac239. The genetic determinants of iMac239's CD4 independence provide new insights into mechanisms that underlie this phenotype. This virus remained replication competent even after its CD4 binding site had been ablated by mutagenesis. As the first truly non-CD4-tropic SIV, lacking the capacity to interact with CD4, iMac239 will provide the unique opportunity to evaluate SIV pathogenesis and host immune responses in the absence of the immunomodulatory effects of CD4(+) T cell targeting and infection.

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The rapid CD4?+?T-lymphocyte decline and human immunodeficiency virus progression in females compared to males.

Publications

The rapid CD4 + T-lymphocyte decline and human immunodeficiency virus progression in females compared to males.

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