SELECTIVE TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VARIANTS TO SCID MICE RECONSTITUTED WITH HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

The relative infectiousness of laboratory and primary human immunodefi ciency virus type 1 (HIV-1) variants was evaluated in in vitro cell cu ltures of peripheral blood mononuclear cells or MT-2 tells and in Hu-P BL-SCID mice. HIVMN and syncytium-inducing primary isolates were prefe rentially transmitted to cells in tissue culture. HIVBa-L and non-sync ytium-inducing (NSI) primary isolates were more infectious in Hu-PBL-S CID mice, Phylogenetic analysis of env sequences derived from the prim ary isolates, from the cell cultures, and from five Hu-PBL-SCID mice w as performed by using methods designed for resolving differences among closely related sequence pairs, This analysis demonstrated preferenti al transmission of an evolutionarily related subset of NSI variants to Hu-PBL-SCID mice. The pattern of selective transmission of a restrict ed range of NSI variants that is observed in the clinical setting is m aintained in Hu-PBL-SCID mice and not in tissue culture systems, The H u-PBL-SCID mouse model system, when used with appropriate phylogenetic analysis methodologies, will be useful for identifying and characteri zing the more infectious HIV-1 variants that should be targeted for va ccine development.