title: Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque.
abstract: High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4⁺ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4⁺ and CD8⁺ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4⁺ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.
authors.affiliation: Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: Margalida
authors.initials: M
authors.lastname: Rotger
authors.forename: Judith
authors.initials: J
authors.lastname: Dalmau
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.forename: Paul
authors.initials: P
authors.lastname: McLaren
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bosinger
authors.forename: Raquel
authors.initials: R
authors.lastname: Martinez
authors.forename: Netanya G
authors.initials: NG
authors.lastname: Sandler
authors.forename: Annelys
authors.initials: A
authors.lastname: Roque
authors.forename: Julia
authors.initials: J
authors.lastname: Liebner
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.forename: Itziar
authors.initials: I
authors.lastname: Erkizia
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Jose M
authors.initials: JM
authors.lastname: Miró
authors.forename: Eduard
authors.initials: E
authors.lastname: Palou
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Marta
authors.initials: M
authors.lastname: Massanella
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
authors.forename: Matthew
authors.initials: M
authors.lastname: Woods
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Paul
authors.initials: P
authors.lastname: de Bakker
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D016665:Cercocebus atys / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D004198:Disease Susceptibility; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D013045:Species Specificity; D015854:Up-Regulation; D019562:Viral Load; D014766:Viremia / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication