Genetically and epidemiologically related "non-syncytium-inducing" isolates of HIV-1 display heterogeneous growth patterns in macrophages

The objective of this study was to identify phenotypic parameters that coul d distinguish among seemingly homogeneous non-syncytium-inducing (NSI) viru ses and that might provide a surrogate marker for clinical progression in p ediatric human immunodeficiency virus type 1 (HIV-1) infection. We undertoo k a pilot analysis of 15 independent HIV-1 isolates collected prospectively from two mothers and their four children who displayed a spectrum of disea se stages ranging from CDC categories Al to C3. Viruses were evaluated for their ability to replicate in primary cells (including monocyte-derived mac rophages [MDM]) and cell lines, for their co-receptor preference and for ge netic features of the V3 hypervariable domain of env. Virtually all isolate s displayed NSI phenotypes that were restricted in their capacity to replic ate in cell lines and displayed V3 loops with uniformly low net positive ch arges. NSI viruses from two symptomatic children and one mother were macrop hage-tropic, whereas NSI isolates from two asymptomatic children were unabl e to replicate in MDM and were designated primary lymphotropic viruses. Onl y one isolate was syncytium-inducing (SI), replicated in a variety of cell lines and in MDM, used multiple co-receptors, and was dual tropic, rather t han a mixture of T-cell tropic and M-tropic viruses, as assessed by genetic analysis. Phenotypic heterogeneity among NSI viruses is revealed in the ab ility of isolates to replicate in MDM. This characteristic is related to di sease stage and provides a potentially new in vitro criterion to distinguis h among NSI isolates that is unlinked to other surrogate markers. (C) 2000 Wiley-Liss, Inc.