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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.date.accessioned2017-06-06T20:06:20Z
dc.date.available2017-06-06T20:06:20Z
dc.date.issued2012-06
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.identifier.urihttp://hdl.handle.net/11721/1641
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.language.isoenen_US
dc.publisherMary Ann Lieberten_US
dc.subject.meshAcquired Immunodeficiency Syndrome/*genetics
dc.subject.meshHIV-1/*pathogenicity
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.meshAdult
dc.subject.meshAnimals
dc.subject.meshCohort Studies
dc.subject.meshDisease Models
dc.subject.meshAnimal
dc.subject.meshFemale
dc.subject.meshHIV-1/isolation & purification
dc.subject.meshHumans
dc.subject.meshHypertension
dc.subject.meshPulmonary/etiology
dc.subject.meshHypertension
dc.subject.meshPulmonary/immunology
dc.subject.meshMacaca mulatta
dc.subject.meshMale
dc.subject.meshMolecular Sequence Data
dc.subject.meshPhylogeny
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.typeArticleen_US
dc.identifier.doi10.1089/aid.2011.0021en_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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