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.
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-1JR-CSF, 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.
Browning Paul
J
J
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Wang
E J
EJ
Pettoello-Mantovani
M
M
Raker
C
C
Yurasov
S
S
Goldstein
M M
MM
Horner
J W
JW
Chan
J
J
Goldstein
H
H
D000818:Animals; D018920:Coculture Techniques; D004768:Enterotoxins / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000097:blood / Q000276:immunology / Q000821:virology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000821:virology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics*; D012367:RNA, Viral / Q000032:analysis; D013210:Staphylococcus / Q000276:immunology; D014611:Vaccination; D014766:Viremia / Q000821:virology; D014779:Virus Replication / Q000235:genetics*
D004768:Enterotoxins; D012367:RNA, Viral