Effects of Reverse-Transcriptase Mutations M184V and E89G on Simian Immunodeficiency Virus in Rhesus Monkeys

• Published in: The Journal of infectious diseases Vol. 184; no. 10; pp. 1262 - 1267
• Main Authors: Newstein, Michael C., Desrosiers, Ronald C.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.11.2001; University of Chicago Press; Oxford University Press
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Cell Line; Cell lines; Codon; Genetic mutation; HIV; HIV 1; Human immunodeficiency virus 1; Human viral diseases; Infections; Infectious diseases; Inoculation; Lymphocytes; Macaca mulatta; Major Articles; Medical sciences; Mutation; Pharmacology. Drug treatments; RNA; RNA-Directed DNA Polymerase - genetics; Sequence Analysis; Simian Acquired Immunodeficiency Syndrome - virology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - physiology; Time Factors; Transfection; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virus Replication - genetics; Viruses; RNA-directed DNA polymerase; HIV-1 virus; Viremia; Monkey; DNA-directed RNA polymerase; Reversion; Codon; Primates; Viral load; Human; Immunopathology; Enzyme; Transferases; Retroviridae; AIDS; Lentivirus; Immune deficiency; Infection; Virus; Resistance; Nucleotidyltransferases; Vertebrata; Mammalia; Viral disease; Human immunodeficiency virus; Mutation; Detection; Simian immunodeficiency virus; Fitness
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/324079

Mutations in human immunodeficiency virus type 1 reverse-transcriptase codons 89 and 184 confer inhibitor resistance and alter the mutation spectrum of the enzyme. Six macaques were inoculated with wild-type or mutated derivatives (E89G or E89G and M184V) of simian immunodeficiency virus macaque (SIVmac) 239. Five of the infected monkeys maintained high virus loads; the sixth, which was infected with the E89G mutant strain, maintained viremia at a level below the limit of detection. Sequence analysis demonstrated substantial reversion of the E89G mutation in the animals with progressive infection and preservation of this mutation in the animal with controlled infection. A P272S mutation occurred at high frequency in the viruses containing M184V, which did not revert. These results demonstrate that the E89G mutation has a significant negative impact on SIVmac fitness, whereas SIVmac bearing M184V achieved high, sustained virus loads, perhaps with a compensatory effect of the P272S mutation