Macaques infected with attenuated simian immunodeficiency virus resist superinfection with virulence-revertant virus

Macaques infected with attenuated simian immunodeficiency virus (SIVmac) can resist superinfection challenge with virulent virus, showing the potential of live attenuated virus as an AIDS vaccine. Superinfection resistance does not, however, prevent the generation of virulent virus in vivo, suggesting that such virus may circumvent the resistance effect. Here, we show that three macaques already infected with the attenuated molecular clone SIVmacC8 were resistant to superinfection with virulent virus that arose in vivo following repair of a 12 bp attenuating lesion in the nef/3' LTR. In contrast, four naive animals became infected following inoculation with blood taken from the macaque in which virulent virus arose. Loss of nef-specific cytotoxic T lymphocyte (CTL) responses followed repair of the attenuating lesion within nef in the donor animal, suggesting the possibility of escape from CTL-driven selection pressure.