Divergent tropism of HHV-6AGS and HHV-6BPL1 in T cells expressing different CD46 isoform patterns

CD46 is a receptor for HHV-6A, but its role as a receptor for HHV-6B is controversial. The significance of CD46 isoforms for HHV-6A and HHV-6B tropism is unknown. HHV-6A(GS) was able to initiate transcription of the viral genes U7 and U23 in the CD46(+)CD134(-) T-cell lines Peer, Jurkat, Molt3, and SupT1, whereas HHV-6B(PL1) was only able to do so in Molt3 and SupT1, which expressed a CD46 isoform pattern different from Peer and Jurkat. The HHV-6B(PL1)-susceptible T-cell lines were characterized by low expression of the CD46 isoform BC2 and domination of isoforms containing the cytoplasmic tail, CYT-1. A HHV-6B(PL1) susceptible cell line, Be13, changed over time its CD46 isoform pattern to resemble Peer and Jurkat and concomitantly lost its susceptibility to HHV-6B(PL1) but not HHV-6A(GS) infection. We propose that isoforms of CD46 impact on HHV-6B infection and thereby in part explain the distinct tropism of HHV-6A(GS) and HHV-6B(PL1).