title: TRIM5α does not affect simian immunodeficiency virus SIV(mac251) replication in vaccinated or unvaccinated Indian rhesus macaques following intrarectal challenge exposure.
abstract: TRIM5α is a natural resistance factor that binds retroviral capsid proteins and restricts virus replication. The B30.2/SPRY domain of TRIM5α is polymorphic in rhesus macaques, and some alleles are associated with reduced simian immunodeficiency virus (SIV) SIV(mac251) and SIV(smE543) replication in vivo. We determined the distribution of TRIM5α alleles by PCR and sequence analysis of the B30.2/SPRY domain in a cohort of 82 macaques. Thirty-nine of these macaques were mock vaccinated, 43 were vaccinated with either DNA-SIV/ALVAC-SIV/gp120, ALVAC-SIV/gp120, or gp120 alone, and all were exposed intrarectally to SIV(mac251) at one of three doses. We assessed whether the TRIM5α genotype of the macaques affected the replication of challenge virus by studying the number of SIV variants transmitted, the number of exposures required, the SIV(mac251) viral level in plasma and tissue, and the CD4(+) T-cell counts. Our results demonstrated that TRIM5α alleles, previously identified as restrictive for SIV(mac251) replication in vivo following intravenous exposure, did not affect SIV(mac251) replication following mucosal exposure, regardless of prior vaccination, challenge dose, or the presence of the protective major histocompatibility complex alleles (MamuA01(+), MamuB08(+), or MamuB017(+)). The TRIM5α genotype had no apparent effect on the number of transmitted variants or the number of challenge exposures necessary to infect the animals. DNA sequencing of the SIV(mac251) Gag gene of the two stocks used in our study revealed SIV(mac239)-like sequences that are predicted to be resistant to TRIM5α restriction. Thus, the TRIM5α genotype does not confound results of mucosal infection of rhesus macaques with SIV(mac251).
authors.affiliation: Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Fenizia
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: David
authors.initials: D
authors.lastname: Nichols
authors.forename: Stefano
authors.initials: S
authors.lastname: Cornara
authors.forename: Nicolò
authors.initials: N
authors.lastname: Binello
authors.forename: Monica
authors.initials: M
authors.lastname: Vaccari
authors.forename: Poonam
authors.initials: P
authors.lastname: Pegu
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Ma
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hirsch
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D016679:Genome, Viral; D018928:Immunity, Mucosal; D008253:Macaca mulatta / Q000276:immunology / Q000378:metabolism / Q000821:virology; D011110:Polymorphism, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D044767:Ubiquitin-Protein Ligases; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014779:Virus Replication
chemical_list: D011506:Proteins; D012367:RNA, Viral; D014765:Viral Vaccines; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases