Genetic immunization with multiple HIV-1 genes provides protection against HIV-1/MuLV pseudovirus challenge in vivo.
Superinfection by HIV-1 of a cell line containing the complete murine leukemia virus (MuLV) genome was shown to give rise to pseudotyped HIV-1/MuLV. Such superinfection was successful with certain strains of HIV-1 subtypes A-D. Primary spleen cells and cells of the peritoneal cavity of immunocompetent mice of the C57Bl/6 strain were infectable with the pseudotype HIV-1/MuLV and secreted HIV-1 in vitro and in vivo. In contrast, the murine cell lines, NIH 3T3, myeloma cell line Sp2/0, and two murine hybridoma cell lines were relatively resistant to infection and produced no or little HIV. After primary murine spleen cells had been infected with pseudotyped HIV-1 and transferred to C57Bl/6 mice, replication-competent HIV-1 was obtained from the peritoneal cavity for at least 10-14 days. High amounts (> 10(5) vRNA copies/ml) of HIV-1 vRNA could be measured in the peritoneal fluid. Presence of HIV-1 proviral DNA was detectable in cells from the peritoneal cavity for up to 24 days after infected cell transfer. Active reverse transcriptase representing both HIV-1 and C-type murine retroviruses was detected in the peritoneal washes. The HIV-infected spleen cells injected into the peritoneal cavity elicited HIV-1-specific cellular immune responses to p24gag, gp160Env, Nef, Tat and Rev. Mice immunized with HIV-1 DNA, but not with HIV-1 protein, cleared their HIV-1-infected cells within 10-14 days after challenge with HIV-1/MuLV-infected syngeneic spleen cells. This novel model system of primarily cellular reactivity to HIV-1-infected cells in vivo may become useful for assaying experimental HIV-1 immunization schedules.
Hinkula
Jorma
J
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Rollman
Erik
E
Lundholm
Peter
P
Benthin
Reinhold
R
Okuda
Kenji
K
Wahren
Britta
B
D000818:Animals; D002460:Cell Line; D004279:DNA, Viral / Q000302:isolation & purification; D005814:Genes, Viral; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D012367:RNA, Viral / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology
D004279:DNA, Viral; D015483:HIV Antibodies; D012367:RNA, Viral; D015847:Interleukin-4; D007371:Interferon-gamma