Mice transgenic for simian immunodeficiency virus nef are immunologically compromised.

Mice transgenic for simian immunodeficiency virus nef are immunologically compromised.

Larsen N B; Kestler H W; Docherty J J

Journal of biomedical science

1998

1998-08

An intact nef gene is essential for rapid development of immunodeficiency in human immunodeficiency virus and simian immunodeficiency virus infections. To assess the role of nef in the immune response, mice transgenic for SIV nef were constructed and the humoral and cellular immune response to herpes simplex virus type-1 (HSV-1), measured. Mice transgenic for SIVmac239 nef exhibited a significantly increased mortality rate when challenged with HSV-1 and also showed unusual antibody kinetics in response to viral challenge. During a 32-week period following exposure to HSV, it was noted that IgG subclass titers continued to rise in the nef+ animals, while titers of nef- animals decreased. Additionally, following secondary challenge with HSV, nef- mice had a significantly greater rise in HSV-neutralizing antibody titers than nef+ mice. A decreased proliferative response to the T cell mitogen, PHA, was noted in the nef+ animals. These results suggest that the presence of nef+ is sufficient to induce immune dysfunction.

*Genes; *Herpesvirus 1; *Immunocompromised Host; 3T3 Cells; Aging; Animals; Antibodies; Antibody Formation; Cellular; Cercopithecus aethiops; Female; Herpes Simplex/*immunology; HIV/pathogenicity; Human; Humans; Immunity; Immunoglobulin G/blood; Kinetics; Male; Mice; nef; Simian Immunodeficiency Virus/*genetics/pathogenicity; Transgenic; Vero Cells; Viral/biosynthesis/blood

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