The positive influence of Nef on viral infectivity

The nef gene is unique to the primate immunodeficiency viruses (HIV1, HIV2 and SIV). Although termed an accessory gene, nef is an important determinant of pathogenesis during experimental infection of adult monkeys and in human disease. In the absence of nef, viral replication in the host is inefficient, CD4-positive T cells are not depleted, and clinical immunodeficiency does not develop. The mechanism by which nef contributes to pathogenesis, however, remains unclear. The positive influence of Nef on viral infectivity is a direct, virologic mechanism for the contribution of this gene product to virulence. Recent data characterizing the dynamics of viral replication in vivo describe a continuous process of viral production, cell death and infection of new target cells. Under these conditions, even a modest decrease in the efficiency of new infection events is predicted to cause a dramatic effect on viral load and consequently on the pathogenesis of disease. The effect of Nef on viral infectivity may exemplify such a process.