Session 25Oral Abstract Presentations Viral Pathogenesis Session Day and Time: Thursday 10 am - 12:30 pm Presentation Time: 11:00 Room: Ballroom A
124 Viral Kinetics of SIV mac251 in Acute Infection: Estimation of the "Basic Reproductive Ratio" Hiroshi Mohri*1, Naureen Mushtaq1, Rudolph Bohm2, Agegnehu Gettie2, Ruy Ribeiro3, Alan S. Perelson3, David D. Ho1 1Aaron Diamond AIDS Res Ctr, New York, NY; 2Tulane Reg Primate Res Ctr, Convington, LA; and 3Los Alamos Natl Lab, NM
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 when almost all cells are uninfected. For a vaccine to prevent infection, R0 has to be driven below 1. Thus, the accurate determination of R0 is important to establish targets for successful vaccination. R0 for HIV-1/SIV has only been estimated from virus in plasma; however, most infection occurs in tissue. To obtain an accurate estimate of R0, we studied viral and infected cell dynamics in blood and lymph nodes (LN) in acute SIV infection.
Methods: Five (5) rhesus macaques were inoculated with 100 TCID50 of SIVmac251 intravenously. Blood was drawn biweekly for the first 3 wks and weekly thereafter. In each monkey, 3 to 5 lymph nodes from different sites were obtained at 3 time points (day 4/5, day 7/8, and day 11) to study the initial exponential growth of the virus. SIV-RNA and SIV-DNA in plasma, PBMC and LN were measured by real time PCR. Infected cell number in PBMC and LN was estimated by end-point dilution nested PCR.
Results: Plasma virus was detectable on day 4 or 5 after the virus inoculation. Plasma virus increased exponentially during the first 2 wk, reached its peak of 2.5 x 107 to 3.7 x 108 copies/ml between days 13 and 18. The up-slope of plasma viral load was 0.83-1.2d-1 (mean 1.0 0.07d-1). The infected cell number in PBMC increased exponentially with up-slope of 0.81-1.6d-1 (1.2 0.19d-1). Infected cells in LN were detectable in some monkeys on day 4 or 5, and in all by day 7 or 8. The infected cell number in LN reached 0.18-3.13/103 cells (1.51 0.53/103 LN cells) on day 11, and the up-slope was 1.1-2.9d-1 (1.9 0.30d-1). We calculate R0 from the observed growth rates, r: R0 = (1 + r/delta)exp(r tau), where tau is the delay between virion entry and virus production and delta is the death rate of infected cells. Assuming delta = 0.74d-1 and tau = 0, we obtain preliminary estimates of R0, between 2.1-2.6 (2.4 0.09) in plasma, and between 3.0-4.8 (3.6 0.41) in a single LN from each monkey; if tau = 1 day, then we get 4.8-8.9 (6.9 0.73) in plasma and 7.6-84 (34 14) in LN.
Conclusions: The R0 values of SIVmac251 in acute infection in plasma and LN were estimated in 5 rhesus macaques. The values in LN are larger than the estimates in plasma SIV and provide a quantitative target for vaccine efficiency. This study also highlights local differences among LN in infected cell growth rates.