TRANSENDOTHELIAL MIGRATION OF LYMPHOCYTES FROM HIV-1-INFECTED DONORS - A MECHANISM FOR EXTRAVASCULAR DISSEMINATION OF HIV-1

To identify factors that cause HIV-1 to establish perivascular foci of infected cells, we studied the transendothelial migration of blood mo nonuclear leukocytes (MNL) from 76 HIV+ patients and 41 controls, The fraction of patients' lymphocytes that migrated across endothelial cel l monolayers in vitro was significantly increased (p less than or equa l to 0.03) compared with that of control donors, Migration of patients ' CD4(+) T cells was particularly enhanced, whereas the migration of m onocytes did not differ between patients and controls, Lymphocyte migr ation correlated with expression of CD11a/CD18 and CD49d/CD29 and with the quantity of TNF-alpha produced as MNLs migrated through the endot helium. Measurement of HIV-1 proviral DNA copies in the patients' MNLs (n = 26) suggested that in half the cases virus-infected cells accumu lated preferentially amidst the migratory leukocytes. We observed the same behavior with normal donor MNLs infected, in vitro, with each of 4 strains of HIV-1. The number of HIV-1 proviral DNA copies per millio n MNLs was 40 to 178 times higher in the migratory population than in the original population added to the endothelium. To test whether only certain strains of HIV-1 stimulate transendothelial migration of infe cted cells, we used single strand conformation polymorphism analysis t o identify quasispecies of HIV-1 in the MNLs. If all strains of HIV-1 were equal in their ability to stimulate transendothelial migration, w e expected to find no differences in the quasispecies present in the o riginal and migratory cell populations, In fact the quasispecies diffe red in 14 of 19 paired samples, suggesting that only certain HIV-1 qua sispecies promote transendothelial migration of infected cells.