Rapid systemic spread and minimal immune responses following SIVsab intrarectal transmission in African green monkeys

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Abstract

African green monkeys (AGMs) are natural hosts of SIV whose infection does not progress to AIDS. Since early events of infection may be critical to pathogenesis in nonnatural hosts, we investigated early SIV infection in 29 adult male AGMs intrarectally inoculated with SIVsab92018 (SIVsab) and serially sacrificed throughout acute into early chronic infection to understand patterns of viral establishment, dissemination, and their effect on disease progression. Using this model, we showed that foci of virus replication could be detected at the site of inoculation and in the draining lymphatics as early as 1–3 days postinfection (dpi). Furthermore, testing with ultrasensitive assays showed rapid onset of viremia (2–4 dpi). After systemic spread, virus was detected in all tissues surveyed. Multiple transmitted/founder viruses were identified, confirming an optimal challenge dose, while demonstrating a moderate mucosal genetic bottleneck. Resident CD4+ T cells were the initial target cells; other immune cell populations were not significantly altered at the site of entry. Thus, intrarectal SIVsab infection is characterized by swift dissemination of the virus, a lack of major target cell recruitment, and no window of opportunity for interventions to prevent virus dissemination during the earliest stages of infection, similar to intrarectal transmission but different from vaginal transmission in macaques.

Authors

Kevin D. Raehtz, Cuiling Xu, Claire Deleage, Dongzhu Ma, Benjamin B. Policicchio, Egidio Brocca-Cofano, Daniele Piccolo, Kathryn Weaver, Brandon F. Keele, Jacob D. Estes, Cristian Apetrei, Ivona Pandrea