An in vitro assay for acute pathogenicity of immunodeficiency viruses.
As a model for AIDS, experimental infections of old-world monkeys with various simian immunodeficiency viruses (SIV) are frequently carried out to study mechanisms of pathogenicity. For example, SIVsmmPBj14 was isolated from a pig-tailed macaque (Macaca nemestrina) suffering from acute viral disease. The molecular virus clone SIVsmmPBj1.9, which displays close genetic homology to other related SIVs, was shown to induce an acute viral disease in vivo after infection of pig-tailed and rhesus macaques. The acute pathogenicity of SIVsmmPBj1.9 was correlated with its unique ability to replicate in non-stimulated peripheral blood mononuclear cells from pig-tailed macaques. We have exploited this in vitro assay to resolve putative pathogenic genetic determinants of another SIV, namelySIVagm3, isolated from African green monkeys (Cercopithecus aethiops). Hybrid viruses encompassing subgenomic regions of SVsmmPBj1.9 in place of comparable regions of molecular virus clone SIVagm3mc were constructed and tested for their ability to replicate in non-stimulated PBMC from pig-tailed macaques and African green monkeys. Only those hybrid viruses comprising the U3 region of the viral LTR of SIVsmmPBj1.9 replicated in non-stimulated peripheral blood mononuclear cells. This in vitro assay will be used to determine the potential of SIV and of hybrid viruses between different SIVs to induce acute viral disease in vivo. It will help to avoid excessive experimental infections of monkeys with respective hybrid viruses for determining genetic determinants of acute pathogenicity of immunodeficiency viruses.
Dittmar
M T
MT
Dept. of Medical Biotechnology, Paul-Ehrlich-Institute, Langen, Germany.
Wagener
S
S
Fultz
P
P
Kurth
R
R
Cichutek
K
K
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology; D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D002678:Chimera; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D016679:Genome, Viral; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000821:virology; D008254:Macaca nemestrina; D011533:Proviruses / Q000235:genetics; D011995:Recombination, Genetic; D016097:Simian Acquired Immunodeficiency Syndrome / Q000209:etiology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence; D014779:Virus Replication