HIV X4 Variants Increase Arachidonate 5-Lipoxygenase in the Pulmonary Microenvironment and are associated with Pulmonary Arterial Hypertension.

Scientific Reports
Sharilyn AlmodovarRoy L Sutliff

Abstract

Pulmonary Arterial Hypertension (PAH) is overrepresented in People Living with Human Immunodeficiency Virus (PLWH). HIV protein gp120 plays a key role in the pathogenesis of HIV-PAH. Genetic changes in HIV gp120 determine viral interactions with chemokine receptors; specifically, HIV-X4 viruses interact with CXCR4 while HIV-R5 interact with CCR5 co-receptors. Herein, we leveraged banked samples from patients enrolled in the NIH Lung HIV studies and used bioinformatic analyses to investigate whether signature sequences in HIV-gp120 that predict tropism also predict PAH. Further biological assays were conducted in pulmonary endothelial cells in vitro and in HIV-transgenic rats. We found that significantly more persons living with HIV-PAH harbor HIV-X4 variants. Multiple HIV models showed that recombinant gp120-X4 as well as infectious HIV-X4 remarkably increase arachidonate 5-lipoxygenase (ALOX5) expression. ALOX5 is essential for the production of leukotrienes; we confirmed that leukotriene levels are increased in bronchoalveolar lavage fluid of HIV-infected patients. This is the first report associating HIV-gp120 genotype to a pulmonary disease phenotype, as we uncovered X4 viruses as potential agents in the pathophysiology of ...Continue Reading

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Citations

Feb 23, 2021·Frontiers in Cellular and Infection Microbiology·Dinesh DevadossMohan Sopori
May 7, 2021·International Heart Journal·Tian-Ming WangYi-Qing Yang

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Methods Mentioned

BETA
transgenic
bronchoalveolar lavage
flow cytometry
PCR
ELISA
bronchoalveolar
lavage
ELISAs

Software Mentioned

GraphPad Prism
Geno2Pheno ( )
SAS
Geno2Pheno
FlowJo
Geneious

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