COMPARATIVE INTERLEUKIN (IL)-2 INTERFERON (IFN)-GAMMA AND IL-4 IL-10 RESPONSES DURING ACUTE INFECTION OF MACAQUES INOCULATED WITH ATTENUATED NEF-TRUNCATED OR PATHOGENIC SIVMAC251 VIRUS/

Comparison of immune responses to infection by a pathogenic or a nonpa thogenic immunodeficiency virus in macaques may provide insights into pathogenetic events leading to simian AIDS, This work is aimed at expl oring cytokine expression during infection by simian immunodeficiency virus (SIV), We used semiquantitative reverse transcription-PCR to mon itor interleukin (IL)-2/interferon (IFN)-gamma (Th1-like), and IL-4/IL -10 (Th2-like) expression in unmanipulated peripheral blood mononuclea r cells (PBMCs), during the acute phase of infection of eight cynomolg us macaques (Macaca fascicularis) with a pathogenic primary isolate of SIVmac251 (full-length nef), and of four other cynomolgus macaques by an attenuated molecular clone of SIVmac251 (nef-truncated). All the m onkeys became infected, as clearly shown by the presence of infected P BMCs and by seroconversion, Nevertheless, PBMC-associated virus loads and p27 antigenemia in monkeys infected by the attenuated virus clone remained lower than those observed in animals infected with the pathog enic SIVmac251 isolate, A rise of IL-10 mRNA expression occurred in bo th groups of monkeys coincident with the peak of viral replication, In monkeys infected with the pathogenic SIVmac251, IL-2, IL-4, and IFN-g amma mRNAs were either weakly detectable or undetectable, On the contr ary, animals infected by the attenuated virus exhibited an overexpress ion of these cytokine mRNAs during the first weeks after inoculation, The lack of expression of these cytokines in monkeys infected with the pathogenic primary isolate may reflect early immunodeficiency.