Persistent infection of rhesus macaques by the Rev-independent Nef(-) simian immunodeficiency virus SIVmac239: Replication kinetics and genomic stability

We generated previously a Nef(-), replication-competent clone of SIVmac239 in which the Rev protein and the Rev-responsive element were replaced by th e constitutive transport element (CTE) of simian retrovirus type 1 (A. S. v on Gegerfelt and B. K. Feliber, Virology 232:291-299, 1997). In the present report, we show that this virus was able to infect and replicate in rhesus macaques. The Rev-independent Nef(-) simian immunodeficiency virus induced a persistent humoral immune response in all monkeys, although viral loads were very low. Upon propagation in the monkeys, the genotype remained stabl e and the virus retained its in vitro growth characteristics. The infected monkeys showed normal hematological values and no signs of disease at more than 18 months post-virus exposure. Therefore, replacement of the essential Rev regulation by the CTE generated a virus variant that retained its repl icative capacity both in vitro and in vivo, albeit at low levels.