TY - JOUR
T1 - Mice transgenic for monocyte-tropic HIV type 1 produce infectious virus and display plasma viremia
T2 - A new in vivo system for studying the postintegration phase of HIV replication
AU - Paul, Jessie Browning
AU - Wang, Emilie Jeanne
AU - Pettoello-Mantovani, Massimo
AU - Raker, Christina
AU - Yurasov, Sergey
AU - Goldstein, Marsha M.
AU - Horner, James W.
AU - Chan, John
AU - Goldstein, Harris
PY - 2000/3/20
Y1 - 2000/3/20
N2 - 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.
AB - 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.
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U2 - 10.1089/088922200309142
DO - 10.1089/088922200309142
M3 - Article
C2 - 10772534
AN - SCOPUS:0034689322
SN - 0889-2229
VL - 16
SP - 481
EP - 492
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
IS - 5
ER -