Full Title: Restricted Replication of Xenotropic Murine Leukemia Virus-Related Virus in Pigtailed Macaques.
Authors: Del Prete GQ, Kearney MF, Spindler J, Wiegand A, Chertova E, Roser JD, Estes JD, Hao XP, Trubey CM, Lara A, Lee K, Chaipan C, Bess JW Jr, Nagashima K, Keele BF, Pung R, Smedley J, Pathak VK, Kewalramani VN, Coffin JM, Lifson JD.
Publication: Journal of Virology
Publication Date: 11th January 2012
AIDS and Cancer Virus Program.
Although Xenotropic Murine Leukemia Virus-related Virus (XMRV) has been previously linked to prostate cancer and myalgic encephalomyelitis/chronic fatigue syndrome, recent data indicate that results interpreted as evidence of human XMRV infection reflect laboratory contamination rather than authentic in vivo infection. Nevertheless, XMRV is a retrovirus of undefined pathogenic potential, able to replicate in human cells. Here, we describe comprehensive analysis of two male pigtailed macaques (Macaca nemestrina) experimentally infected with XMRV. Following intravenous inoculation with >10(10) RNA copy equivalents of XMRV, viral replication was limited and transient, peaking at ≤2200 viral RNA (vRNA) copies/ml plasma and becoming undetectable by 4 weeks postinfection, though viral DNA (vDNA) in PBMC remained detectable through 119 days of follow-up. Similarly, vRNA was not detectable in LN by in situ hybridization (ISH) despite detectable vDNA. Sequencing of cell-associated vDNA revealed extensive G-to-A hypermutation, suggestive of APOBEC-mediated viral restriction. Consistent with limited viral replication, we found transient upregulation of type I IFN responses that returned to baseline by 2 weeks postinfection, no detectable cellular immune responses, and limited or no spread to prostate tissue. Antibody responses, including neutralizing antibodies, however, were detectable by 2 weeks postinfection and maintained throughout the study. Both animals were healthy for the duration of follow-up. These findings indicate that XMRV replication and spread were limited in pigtailed macaques, predominantly by APOBEC-mediated hypermutation. Given that human APOBEC proteins restrict XMRV infection in vitro, human XMRV infection, if it occurred, would be expected to be characterized by similarly limited viral replication and spread.
View the abstract in PubMed.