The MA (p15) and p12 regions of the gag gene are sufficient for the pathogenicity of the murine AIDS virus.
Inoculation of the replication-defective retrovirus DEF27 (BM5d), packaged as an amphotropic virus pseudotype, into C57BL/6J mice leads to development of murine AIDS. Disease development showed a long incubation period (20 to 24 weeks), was associated with amplification of the BM5d provirus in splenocytes and lymph nodes, and was independent of the presence of exogenous or endogenous replication-competent helper viruses. However, both the onset of disease and amplification of the defective provirus were significantly enhanced by coinfection with the replication-competent B-cell-tropic ecotropic helper virus BM5e. The part of the BM5d viral genome that was essential for the pathogenicity was determined by making precisely engineered alterations in the reading frame of the gag and pol genes of BM5d proviral DNA and examining the ability of the altered amphotropic BM5d pseudotypes to induce the disease in C57BL/6J mice. The results show that expression of the MA (p15) and p12 regions of the gag gene is sufficient for pathogenicity of the BM5d retrovirus.
Pozsgay
J M
JM
Oncology Center, Johns Hopkins University, Baltimore, Maryland 21231.
Beilharz
M W
MW
Wines
B D
BD
Hess
A D
AD
Pitha
P M
PM
D000818:Animals; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D003673:Defective Viruses / Q000235:genetics* / Q000472:pathogenicity; D015683:Gene Products, gag / Q000096:biosynthesis / Q000302:isolation & purification; D015750:Genes, gag; D016679:Genome, Viral; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016183:Murine Acquired Immunodeficiency Syndrome / Q000382:microbiology*; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D013154:Spleen / Q000382:microbiology; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
D004279:DNA, Viral; D015683:Gene Products, gag; D009838:Oligodeoxyribonucleotides; D012194:RNA-Directed DNA Polymerase