Susceptibility of rat-derived cells to replication by human immunodeficiency virus type 1

Progress in developing a small animal model of human immunodeficiency virus type 1 (HIV-1) disease would greatly facilitate studies of transmission, p athogenesis, host immune responses, and antiviral strategies. In this study , we have explored the potential of rats as a susceptible host. In a single replication cycle, rat cell lines Rat2 and Nb2 produced infectious virus a t levels 10- to 60-fold lower than those produced by human cells. Rat-deriv ed cells supported substantial levels of early HIV-1 gene expression, which was further enhanced by overexpression of human cyclin Tl. Rat cells displ ayed quantitative, qualitative, and cell-type-specific limitations in the l ate phase of the HIV-1 replication cycle including relative expression leve ls of HIV-1 Gag proteins, intracellular Gag processing, and viral egress. N b2 cells were rendered permissive to HIV-1 R5 viruses by coexpression of hu man CD4 and CCR5, indicating that the major restriction on HIV-1 replicatio n was at the level of cellular entry. We also found that primary rat lympho cytes, macrophages, and microglia expressed considerable levels of early HI V-1 gene products following infection with pseudotyped HIV-1. Importantly, primary rat macrophages and microglia, but not lymphocytes, also expressed substantial levels of HIV-1 p24 CA and produced infectious virions. Collect ively, these results identify the rat as a promising candidate for a transg enic small animal model of HIV-1 infection and highlight pertinent cell-typ e-specific restrictions that are features of this species.