Molecular and biological interactions between two HIV-1 strains from a coinfected patient reveal the first evidence in favor of viral synergism

An intravenous drug user was found to be dually infected with two genetical ly and phylogenetically distinct human immunodeficiency virus type 1 (HIV-1 ) subtype B strains (designated groups I and II). Viral isolation revealed a simultaneous copassaging of two strains in PBMC. The culture of viral str ains on monocytes and monocyte-derived macrophages preferentially segregate d the two viral strains. The group I strain utilized CXCR4 and group II use d CCR5 coreceptor for entry. Sequencing of >100 clones from uncultured PBMC consistently showed the predominance of group II virus in vivo. Importantl y, the group II virus alone could not productively infect PBMC, but when us ed together with group I virus for infection, the group II virus regained i ts high replication potential and predominance in cultured PBMC. These data are the first to provide direct evidence in favor of molecular and biologi cal interaction between two infecting strains in a coinfected patient and s how their differential pathogenic effects, tropism, and modes of entry. In addition, our data provide the first evidence for synergism between these t wo strains. Cumulatively, these data emphasize that in order to clearly int erpret coreceptor usage, biological segregation of viral strains from prima ry isolates in vitro may be imperative. (C) 2000 Academic Press.