Genetic immunization with multiple HIV-1 genes provides protection against HIV-1/MuLV pseudovirus challenge in vivo

Cells Tissues Organs. 2004;177(3):169-84. doi: 10.1159/000079991.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA, Viral / isolation & purification
  • Genes, Viral*
  • HIV Antibodies / biosynthesis
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • HIV-1 / genetics*
  • HIV-1 / immunology*
  • HIV-1 / pathogenicity
  • Humans
  • Immunization
  • In Vitro Techniques
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Leukemia Virus, Murine / genetics*
  • Leukemia Virus, Murine / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • NIH 3T3 Cells
  • RNA, Viral / isolation & purification
  • T-Lymphocytes / immunology

Substances

  • DNA, Viral
  • HIV Antibodies
  • RNA, Viral
  • Interleukin-4
  • Interferon-gamma