Importance of the nef gene for maintenance of high virus loads and for development of AIDS

HW Kestier III, DJ Ringler, K Mori, DL Panicali… - Cell, 1991 - cell.com
HW Kestier III, DJ Ringler, K Mori, DL Panicali, PK Sehgal, MD Daniel, RC Desrosiers
Cell, 1991cell.com
When rhesus monkeys were infected with a form of cloned SIVmac239 having a premature
stop signal at the 93rd codon of nef, revertants with a coding codon at this position quickly
and universally came to predominate in the infected animals. This suggests that there are
strong selective forces for open functional forms of nef in vivo. Although deletion of net
sequences had no detectable effect on virus replication in cultured cells, deletion of nef
sequences dramatically altered the properties of virus in infected rhesus monkeys. Our …
Summary
When rhesus monkeys were infected with a form of cloned SIVmac239 having a premature stop signal at the 93rd codon of nef, revertants with a coding codon at this position quickly and universally came to predominate in the infected animals. This suggests that there are strong selective forces for open functional forms of nef in vivo. Although deletion of net sequences had no detectable effect on virus replication in cultured cells, deletion of nef sequences dramatically altered the properties of virus in infected rhesus monkeys. Our results indicate that nef is required for maintaining high virus loads during the course of persistent infection in vivo and for full pathologic potential. Thus, nef should become a target for antiviral drug development. Furthermore, the properties of virus with a deletion in nef suggest a means for making liveattenuated strains of virus for experimental vaccine testing.
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