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dc.contributor.authorAlmodovar, Sharilyn
dc.contributor.authorKnight, Rob
dc.contributor.authorAllshouse, Amanda A.
dc.contributor.authorRoemer, Sarah
dc.contributor.authorLozupone, Catherine
dc.contributor.authorMcDonald, Daniel
dc.contributor.authorWidmann, Jeremy
dc.contributor.authorVoelkel, Norbert F.
dc.contributor.authorShelton, Robert J.
dc.contributor.authorSuárez- Martínez, Edu B.
dc.contributor.authorHammer, Kenneth W.
dc.contributor.authorGoujard, Cecile
dc.contributor.authorPetrosillo, Nicola
dc.contributor.authorSimonneau, Gerald
dc.contributor.authorHsue, Priscilla Y.
dc.contributor.authorHumbert, Marc
dc.contributor.authorFlores, Sonia C.
dc.identifier.citationAlmodovar S, Knight R, Allshouse AA, et al. Human Immunodeficiency Virus nef Signature Sequences Are Associated with Pulmonary Hypertension. AIDS Research and Human Retroviruses. 2012;28(6):607-618. doi:10.1089/aid.2011.0021.en_US
dc.description.abstractSevere pulmonary hypertension (PH) associated with vascular remodeling is a long-term complication of HIV infection (HIV-PH) affecting 1/200 infected individuals vs. 1/200,000 frequency in the uninfected population. Factors accounting for increased PH susceptibility in HIV-infected individuals are unknown. Rhesus macaques infected with chimeric SHIVnef virions but not with SIV display PH-like pulmonary vascular remodeling suggesting that HIV-Nef is associated with PH; these monkeys showed changes in nef sequences that correlated with pathogenesis after passage in vivo. We further examined whether HIV-nef alleles in HIV-PH subjects have signature sequences associated with the disease phenotype. We evaluated specimens from participants with and without HIV-PH from European Registries and validated results with samples collected as part of the Lung-HIV Studies in San Francisco. We found that 10 polymorphisms in nef were overrepresented in blood cells or lung tissue specimens from European HIV-PH individuals but significantly less frequent in HIV-infected individuals without PH. These polymorphisms mapped to known functional domains in Nef. In the validation cohort, 7/10 polymorphisms in the HIV-nef gene were confirmed; these polymorphisms arose independently from viral load, CD4+ T cell counts, length of infection, and antiretroviral therapy status. Two out of 10 polymorphisms were previously reported in macaques with PH-like pulmonary vascular remodeling. Cloned recombinant Nef proteins from clinical samples down-regulated CD4, suggesting that these primary isolates are functional. This study offers new insights into the association between Nef polymorphisms in functional domains and the HIV-PH phenotype. The utility of these polymorphisms as predictors of PH should be examined in a larger population.en_US
dc.publisherMary Ann Lieberten_US
dc.subject.meshAcquired Immunodeficiency Syndrome/*genetics
dc.subject.meshHypertension, Pulmonary/*genetics
dc.subject.meshSimian Acquired Immunodeficiency Syndrome/*genetics
dc.subject.meshSimian Immunodeficiency Virus/*pathogenicity
dc.subject.meshnef Gene Products, Human Immunodeficiency Virus/*genetics
dc.subject.meshAcquired Immunodeficiency Syndrome/complications
dc.subject.meshAcquired Immunodeficiency Syndrome/immunology
dc.subject.meshCohort Studies
dc.subject.meshDisease Models
dc.subject.meshHIV-1/isolation & purification
dc.subject.meshMacaca mulatta
dc.subject.meshMolecular Sequence Data
dc.subject.meshSan Francisco
dc.subject.meshSimian Acquired Immunodeficiency Syndrome/complications
dc.subject.meshSimian Acquired Immunodeficiency Syndrome/immunology
dc.subject.meshSimian Immunodeficiency Virus/isolation & purification
dc.subject.meshViral Regulatory and Accessory Proteins/genetics
dc.subject.meshVirus Replication/genetics
dc.titleHuman immunodeficiency virus nef signature sequences are associated with pulmonary hypertensionen_US
dc.local.DepartmentDepartment of Biologyen_US
dc.local.FacultySelect from the list belowen_US
dc.contributor.campusUniversity of Puerto Rico at Ponce

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