Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques
Giavedoni, Luis D.
Long, Carlin S.
Voelkel, Norbert F.
Edwards, Michael G.
Folkvord, Joy M.
Westmoreland, Susan V.
Luciw, Paul A.
Flores, Sonia C.
AffiliationUniv Arizona, Coll Med, Dept Med, Div Infect Dis
MetadataShow full item record
PublisherMARY ANN LIEBERT, INC
CitationSharilyn Almodovar, Jessica Swanson, Luis D. Giavedoni, Sreetharan Kanthaswamy, Carlin S. Long, Norbert F. Voelkel, Michael G. Edwards, Joy M. Folkvord, Elizabeth Connick, Susan V. Westmoreland, Paul A. Luciw, and Sonia C. Flores. Viral Immunology. Apr 2018. http://doi.org/10.1089/vim.2017.0051
RightsCopyright © 2018, Mary Ann Liebert, Inc.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractFatal pulmonary arterial hypertension (PAH) affects HIV-infected individuals at significantly higher frequencies. We previously showed plexiform-like lesions characterized by recanalized lumenal obliteration, intimal disruption, medial hypertrophy, and thrombosis consistent with PAH in rhesus macaques infected with chimeric SHIVnef but not with the parental SIVmac239, suggesting that Nef is implicated in the pathophysiology of HIV-PAH. However, the current literature on non-human primates as animal models for SIV(HIV)-associated pulmonary disease reports the ultimate pathogenic pulmonary outcomes of the research efforts; however, the variability and features in the actual disease progression remain poorly described, particularly when using different viral sources for infection. We analyzed lung histopathology, performed immunophenotyping of cells in plexogenic lesions pathognomonic of PAH, and measured cardiac hypertrophy biomarkers and cytokine expression in plasma and lung of juvenile SHIVnef-infected macaques. Here, we report significant hematopathologies, changes in cardiac biomarkers consistent with ventricular hypertrophy, significantly increased levels of interleukin-12 and GM-CSF and significantly decreased sCD40L, CCL-2, and CXCL-1 in plasma of the SHIVnef group. Pathway analysis of inflammatory gene expression predicted activation of NF-B transcription factor RelB and inhibition of bone morphogenetic protein type-2 in the setting of SHIVnef infection. Our findings highlight the utility of SHIVnef-infected macaques as suitable models of HIV-associated pulmonary vascular remodeling as pathogenetic changes are concordant with features of idiopathic, familial, scleroderma, and HIV-PAH.
Note12 month embargo; published online: 1 April 2018
VersionFinal accepted manuscript
SponsorsNIH/NHLBI [R01 HL083491, R01 HL059785, T32-HL007171]; NIH/NCATS [UL1 TR001082, R01 AI096966, R56 AI080418]; NIH Base Operating Grant [OD011107]; NIH/NCRR [P51 RR000168, RR000169]; [OD011133]