title: Susceptibility to repeated, low-dose, rectal SHIVSF162P3 challenge is independent of TRIM5 genotype in rhesus macaques.
abstract: Infections following repeated, low-dose (RLD), mucal S(H)IV exposures of macaques are used to model sexual HIV exposures for biomedical prevention testing. Different susceptibilities among animals can complicate study designs. In rhesus macaques, TRIM5 alleles Q, CypA, and TFP are resistance factors for infection with some S(H)IV strains, but not for SIVmac239 due to its capsid properties. SIVmac239-derived SHIVSF162P3 has been demonstrated to reproducibly infect mucosally in vaginal and rectal RLD models. To further test the suitability of SHIVSF162P3 for RLD models, we studied the influence of the TRIM5 genotype on susceptibility to rectal RLD infection and on plasma viremia by analyzing 43 male Indian rhesus macaques from control arms of completed studies. The median number of exposures required for infection was three (Q/Q, n=4) (TRIM5 alleles, number of macaques, respectively), four (Q/CypA, n=7), three (TFP/Q, n=15), three (TFP/TFP, n=15), and two (TFP/CypA, n=2); TRIM5(CypA/CypA) was not represented in our study. Median peak viremia (log10 viral copies/ml) in infected animals was 7.4 (Q/Q, n=4), 7.2 (Q/CypA, n=6), 7.3 (TFP/Q, n=13), 7.1 (TFP/TFP, n=15), and 6.5 (TFP/CypA; n=2). Neither susceptibility nor peak viremia was significantly different (log rank test, Kruskal-Wallis test, respectively). Rhesus macaques' susceptibility to RLD SHIVSF162P3 is independent of the TRIM5 TFP, CypA, and Q alleles, with the limitation that the power to detect any impact of CypA/CypA and TFP/CypA genotypes was nonexistent or low, due to absence or infrequency, respectively. The finding that TRIM5 alleles do not restrict mucosal infection or ensuing replication rates suggests that SHIVSF162P3 is indeed suitable for RLD experimentation.
authors: Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Katherine
authors: K
authors: Butler
authors: Jennifer S
authors: JS
authors: Morgan
authors: Debra L
authors: DL
authors: Hanson
authors: Debra
authors: D
authors: Adams
authors: J Gerardo
authors: JG
authors: Garcia-Lerma
authors: Walid
authors: W
authors: Heneine
authors: Dennis
authors: D
authors: Ellenberger
authors: R Michael
authors: RM
authors: Hendry
authors: Janet
authors: J
authors: McNicholl
authors: Welkin E
authors: WE
authors: Johnson
authors: Ellen N
authors: EN
authors: Kersh
mesh_terms: D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000635:transmission; D054884:Host-Pathogen Interactions / Q000235:genetics; D007413:Intestinal Mucosa / Q000821:virology; D008253:Macaca mulatta / Q000235:genetics* / Q000821:virology*; D008297:Male; D012007:Rectum / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000235:genetics / Q000635:transmission; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D014766:Viremia / Q000209:etiology / Q000235:genetics
chemical_list: D002352:Carrier Proteins