Replicative capacity, cytopathic effect and cell tropism of HIV

Abstract

Naturally occurring HIV variants show distinct biologic features that correspond to the severity of HIV infection. Virus from asymptomatic HIV carriers or individuals with mild disease replicates slowly and inefficiently in the patients' peripheral blood mononuclear cell cultures. Attempts to passage these viruses in CD4-positive cell lines usually fail or result in transient replication only. In contrast, viruses from patients with severe immunodeficiency replicate rapidly and efficiently in peripheral blood mononuclear cell cultures as well as cell lines: hence the designation slow/low and rapid/high, respectively. These two groups of viruses can also be distinguished by the type of cytopathogenicity exerted in peripheral blood mononuclear cells. Rapid/high viruses are characterized by extensive syncytia formation, whereas syncytia are rarely seen with slow/low viruses. Instead cultures infected with slow/low viruses show signs of cell death or no cytopathic changes at all. It has also been observed that shift from the slow/low type of virus to rapid/high may occur in the same individual over time. Whether this change signals the emergence of HIV variants with increased virulence or reflects the damage to the immune system that can no longer control virus replication remains to be seen. Rapid/high and slow/low viruses can also be distinguished by cell tropism when tested in a model system on indicator cell lines of T-lymphoid or monocytoid origin. Infection by rapid/high viruses activates chloramphenicol acetyl transferase in both T-lymphoid and monocytoid indicator cells, whereas slow/low viruses activate chloramphenicol acetyl transferase only in monocytoid cell lines. A difference between slow/low and rapid/high viruses cannot be demonstrated in fresh normal macrophage cultures, since most isolates can be successfully passaged in macrophages. Whether the viruses that infect macrophages are truly macrophage-tropic or dual-tropic, and infect macrophages and lymphocytes with equal efficiency, remains to be studied.