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

O. T. Keppler, W. Yonemoto, F. J. Welte, K. S. Patton, D. Iacovides, R. E. Atchison, T. Ngo, D. L. Hirschberg, R. F. Speck, M. A. Goldsmith

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Progress in developing a small animal model of human immunodeficiency virus type 1 (HIV-1) disease would greatly facilitate studies of transmission, pathogenesis, 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 at levels 10- to 60-fold lower than those produced by human cells. Rat-derived cells supported substantial levels of early HIV-1 gene expression, which was further enhanced by overexpression of human cyclin T1. Rat cells displayed quantitative, qualitative, and cell-type-specific limitations in the late phase of the HIV-1 replication cycle including relative expression levels of HIV-1 Gag proteins, intracellular Gag processing, and viral egress. Nb2 cells were rendered permissive to HIV-1 R5 viruses by coexpression of human CD4 and CCR5, indicating that the major restriction on HIV-1 replication was at the level of cellular entry. We also found that primary rat lymphocytes, macrophages, and microglia expressed considerable levels of early HIV-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. Collectively, these results identify the rat as a promising candidate for a transgenic small animal model of HIV-1 infection and highlight pertinent cell-type-specific restrictions that are features of this species.

Original languageEnglish
Pages (from-to)8063-8073
Number of pages11
JournalJournal of Virology
Volume75
Issue number17
DOIs
Publication statusPublished - 2001

Fingerprint Dive into the research topics of 'Susceptibility of rat-derived cells to replication by human immunodeficiency virus type 1'. Together they form a unique fingerprint.

  • Cite this

    Keppler, O. T., Yonemoto, W., Welte, F. J., Patton, K. S., Iacovides, D., Atchison, R. E., Ngo, T., Hirschberg, D. L., Speck, R. F., & Goldsmith, M. A. (2001). Susceptibility of rat-derived cells to replication by human immunodeficiency virus type 1. Journal of Virology, 75(17), 8063-8073. https://doi.org/10.1128/JVI.75.17.8063-8073.2001