Evidence for differences in MT2 cell tropism according to genetic subtypes of HIV-1: syncytium-inducing variants seem rare among subtype C HIV-1 viruses.

Abstract

Non-syncytium-inducing (NSI) variants seem to be more readily transmitted than syncytium-inducing (SI) variants, and the switch from NSI to SI during HIV-1 infection seems to be a key determinant to the evolution of AIDS. We investigated eventual differences in the SI capacity on MT-2 cells according to genetic subtypes of HIV-1 and correlated this observations with CD4 counts and duration of HIV infection. In total, 86 patients, most with known date of HIV contamination and infected with different genetic subtypes, have been studied: 11 subtype A, 46 subtype B, 22 subtype C, and 7 subtype E. Multivariate analysis used a Cox's proportional hazards regression. The number and percentage of patients infected with an SI strain were as follows: 3 of 11 (27%) for subtype A, 15 of 46 (33%) for subtype B, 0 of 22 (0%) for subtype C, and 5 of 7 (71%) for subtype E. After adjustment for time after seroconversion and CD4 counts, significantly fewer SI variants were observed in patients infected with subtype C (p < .002) and it was found that subjects infected with subtype E had a higher risk of being infected with an SI strain (rate ratio [RR] = 12.39%; 95% confidence interval [CI] 1.55-98.67; p < .001). Most of the subtype E-infected patients from our study switched from an NSI to SI phenotype early after seroconversion (<4 years). To predict the in vitro presence of SI variants, we scanned V3-loop sequences for mutations at positions 11 and/or 25. Overall, 54 of 55 (98.2%) NSI strains in vitro were predicted NSI, and only 4 of 12 (33.3%) of SI viruses were predicted SI. For patients in whom a switch from an NSI to an SI virus was observed, the SI phenotype could be detected earlier in vitro than by the corresponding V3-loop sequence. No SI strains were observed among patients infected with subtype C; however, longer follow-up is needed to see whether the appearance of SI variants in subtype E or the absence of SI variants in subtype C-infected patients is also associated respectively with a faster or slower progression to AIDS as described for subtype B.