Mice transgenic for monocyte-tropic HIV type 1 produce infectious virus and display plasma viremia: A new in vivo system for studying the postintegration phase of HIV replication

Jessie Browning Paul, Emilie Jeanne Wang, Massimo Pettoello-Mantovani, Christina Raker, Sergey Yurasov, Marsha M. Goldstein, James W. Horner, John Chan, Harris Goldstein

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

To generate an in vivo system for investigating the postintegration phase of HIV-1 replication, mouse lines transgenic for a full-length infectious proviral clone of a monocyte-tropic HIV-1 isolate, HIV-1(JR-SCF), were constructed. Leukocytes from two independent JR-CSF transgenic mouse lines produced HIV-1 that infected human PBMCs. Plasma viremia was detected in these mice at levels (mean, >60,000 HIV RNA copies/ml) comparable to those reported for HIV-1-infected individuals. The levels of HIV RNA in these mice increased several-fold after either treatment with the superantigen Staphylococcus enterotoxin B or infection with Mycobacterium tuberculosis. Thus, a provirus encoding a monocyte-tropic HIV-1 strain under the control of its LTR expressed as a transgene in mice can proceed through the postintegration replication phase and produce infectious virus. In addition, the presence of plasma viremia that can be monitored by measuring plasma HIV- 1 RNA levels permits these mice to be used to study the impact of different interventions on modulating in vivo HIV-1 production. Therefore, these mice provide a novel manipulable system to investigate the in vivo regulation of HIV-1 production by factors that activate the immune system. Furthermore, this murine system should be useful in delineating the role of human-specific factors in modulating HIV-1 replication and investigating the in vivo therapeutic efficacy of agents that target the postintegration stages of HIV- 1 replication.

Original languageEnglish (US)
Pages (from-to)481-492
Number of pages12
JournalAIDS Research and Human Retroviruses
Volume16
Issue number5
DOIs
StatePublished - Mar 20 2000

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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