Analysis of SIV Spatiotemporal Dissemination Patterns in Rhesus Macaques During Early Rectal Transmission Demonstrates Systemic Infection Does Not Require Viral Local Amplification at the Entry Portal

Abstract

Receptive anal sex is a dominant mode of HIV-1 (HIV) transmission, especially among men who have sex with men (MSM). However, the early events during HIV rectal transmission are not well understood and many questions remain, such as, does virus local amplification at the entry portal require for viral distal seeding? What is the spatiotemporal dissemination pattern across whole body? How do three viral forms, i.e., cell-free virus (VCF), cell-associated virus (VCA), and follicular dendritic cell-trapped virus (VFDC), evolve during early infections? To close this knowledge gap, we comprehensively examined rectum, draining lymph nodes (dLN) and distal lymph nodes (disLN), as well as non-lymphoid organs of brain, lungs, and liver of Indian rhesus macaques (RMs) at the early time points following intrarectal SIVmac251 inoculation (1, 2, 3, 4, 6, 10 14, 28 day post inoculation, dpi). Our findings demonstrated SIV rapidly disseminates to distant tissues and organs (<=1 dpi) and virus local amplification in rectum and dLN is not required for viral distal seeding for the establishment of systemic infection, viral forms shift from VCF and VCA to VFDC accompanying from T cell zones into B cell follicles. Collectively, these findings indicate that an effective HIV vaccine needs to induce immune protection both locally at sites of viral entry and systemically.