IN-VIVO DISTRIBUTION AND CYTOPATHOLOGY OF VARIANTS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SHOWING RESTRICTED SEQUENCE VARIABILITY IN THE V3LOOP

The distribution, cell tropism, and cytopathology in vivo of human imm unodeficiency virus (HIV) was investigated in postmortem tissue sample s from a series of HIV-infected individuals who died either of complic ations associated with AIDS or for unrelated reasons while they were a symptomatic. Proviral sequences were detected at a high copy number in lymphoid tissue of both presymptomatic patients and patients with AID S, whereas significant infection of nonlymphoid tissue such as that fr om brains, spinal cords, and lungs was confined to those with AIDS. V3 loop sequences from both groups showed highly restricted sequence var iability and a low overall positive charge of the encoded amino acid s equence compared with those of standard laboratory isolates of HN type 1 (HIV-1). The low charge and the restriction in sequence variability were comparable to those observed with isolates showing a non-syncyti um-inducing (NSI) and macrophage-tropic phenotype in vitro. All patien ts were either exclusively infected (six of seven cases) or predominan tly infected (one case) with variants with a predicted NSI/macrophage- tropic phenotype, irrespective of the degree of disease progression. p 24 antigen was detected by immunocytochemical staining of paraffin-fix ed sections in the germinal centers within lymphoid tissue, although l ittle or no antigen was found in areas of lymph node or spleen contain ing T lymphocytes from either presymptomatic patients or patients with AIDS. The predominant p24 antigen-expressing cells in the lungs and b rains of the patients with AIDS were macrophages and microglia (in bra ins), frequently forming multinucleated giant cells (syncytia) even th ough the V3 loop sequences of these variants resembled those of NSI is olates in vitro. These studies indicate that lack of syncytium-forming ability in established T-cell lines does not necessarily predict sync ytium-forming ability in primary target cells in vivo. Furthermore, va riants of HN with V3 sequences characteristic of NSI/macrophage-tropic isolates form the predominant population in a range of lymphoid and n onlymphoid tissues in vivo, even in patients with AIDS.