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

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, e.g., cell-free virus (V _CF ), cell-associated virus (V _CA ), and follicular dendritic cell-trapped virus (V _FDC ), evolve during early infections? To close this knowledge gap, we comprehensively examined rectum, draining and distant lymph nodes, as well as non-lymphatic organs of brain, lungs, and liver of 39 Indian rhesus macaques at the early time points following intrarectal SIV inoculation (1, 2, 3, 4, 6, 10 14, 28 day post inoculation, dpi). Our findings unambiguously demonstrated SIV rapidly disseminates to distant tissues and organs (<=1 dpi), virus local replication and amplification in rectum and draining lymph nodes are not required for viral distal seeding for the establishment of systemic infection, viral forms shift from V _CF and V _CA to V _FDC accompanying from T-cell zones into B-cell follicles. These findings indicates that an effective HIV vaccine needs to elicit comprehensive immune protection locally at sites of viral entry as well as systemically.