Background: Early viral kinetics can be characterized by the 'basic reproductive ratio', R₀, the average number of cells infected by the progeny of an infected cell. We previously reported that the viral replication in lymph nodes was faster than in plasma and PBMC (R₀ was 16.7 vs. 5.6 and 6.3, respectively) when rhesus macaques were infected with SIVmac251 intravenously. We have extended our study to the viral kinetics of SHIV162P3 infection, and to the viral kinetics following mucosal infection, the most common route of HIV-1 transmission.

Methods: Four rhesus macaques were inoculated with 100 TCID₅₀ of SHIV162P3 intravenously (IV). For a mucosal infection, one rhesus macaque was inoculated with 6,400 TCID₅₀ intravaginally (IVAG), and three rhesus macaques with 500 TCID₅₀ together with progesterone pretreatment. Blood was drawn biweekly or weekly. In each monkey, 3 to 4 lymph nodes from different sites were obtained at 3 to 4 time points to study the initial exponential growth of the virus. SIV-RNA in plasma was measured by real time PCR. Infected cell number in LN was estimated by end-point dilution nested PCR. Productively infected cell number in LN was measured by in situ hybridization method in selected cases.

Results: Plasma virus was detectable on day 4 after IV inoculation with SHIV162P3. Plasma virus increased exponentially during the first 13 days. The mean up-slope (±SE) of plasma viral load was 1.6 ± 0.07d^-1 (R₀ = 12.9 ± 1.31). Infected cells in LN were detectable in some LNs on day 4, and in all by day 7 and the mean up-slope was 2.4 ± 0.32d^-1 (R₀ = 48.3 ± 19.63). These results indicated that SHIV162P3 spreads much faster than SIVmac251. In IVAG infection with SIVmac251, plasma virus was detected on day 7 to 14, which was delayed compared to IV infection (day 4 or 5). The mean up-slope of plasma viral load was 1.1 ± 0.12d^-1 (R₀ = 6.7 ± 1.33). Infected cells in LN were detectable in some LNs on day 10 or 11, and in most by day 13 or 14 and the mean up-slope was 1.2 ± 0.15d^-1 (R₀ = 8.3 ± 1.83). These results indicate that in mucosal infection, early viral kinetics may delay, probably, due to local viral replication before establishing systemic infection.

Conclusions: The R₀ values of SHIV162P3 (IV) and SIVmac251 (IVAG) in acute infection in plasma and LN were estimated, which provide a quantitative target for vaccine efficiency. This study also highlights local differences among LNs in infected cell growth rates.

Keywords: viral kinetics; R0; SIV/SHIV