Quantification system for the viral dynamics of a highly pathogenic simian/human immunodeficiency virus based on an in vitro experiment and a mathematical model

We infected HSC-F cells with SHIV-KS661 and measured the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for nine days. The experiments were repeated at four different MOIs, and the model was fitted to the full dataset simultaneously. Our analysis allowed us to extract an infected cell half-life of 14.1 h, a half-life of SHIV-KS661 infectiousness of 17.9 h, a virus burst size of 22.1 thousand RNA copies or 0.19 TCID50, and a basic reproductive number of 62.8. Furthermore, we calculated that SHIV-KS661 virus-infected cells produce at least 1 infectious virion for every 350 virions produced.Our method, combining in vitro experiments and a mathematical model, provides detailed quantitative insights into the kinetics of the SHIV infection which could be used to significantly improve the understanding of SHIV and HIV-1 pathogenesis. The method could also be applied to other viral infections and used to improve the in vitro determination of the effect and efficacy of antiviral compounds.Historically, the study of the highly pathogenic simian/human immunodeficiency virus (SHIV) has provided important information for the understanding of human immunodeficiency virus type-1 (HIV-1) pathogenesis. For example, it was clarified in an SHIV animal study that co-receptor usage determined by the HIV-1 env gene affects the virus' cell tropism (preference for specific target cell populations), and thus its pathogenesis, in vivo [1-3]. Furthermore, infections with highly pathogenic SHIV strains in animal models have exhibited stable clinical manifestations in most infected animals, similar to an aspect of infection course in human HIV infections [4,5]. One of the highly pathogenic SHIV strains, SHIV-KS661, which has the env gene of HIV-1 89.6 and predominantly uses CXCR4 as the secondary receptor for its infection [2], causes an infection that systemically depletes the CD4+ T cells of rhesus maca