Glycoproteins M and N of human herpesvirus 8 form a complex and inhibit cell fusion.

Glycoproteins M (gM) and N (gN) are well conserved across the herpesvirus family and their involvement in virus penetration and egress is well described, especially for alphaherpesviruses. Because there was no previous study on the homologues of human herpesvirus 8 glycoproteins M (gM8) and N (gN8), we analysed their biochemical and functional characteristics. We found that: (i) gM8 aggregated following heat treatment; (ii) gM8 was a virion component; (iii) gM8 and gN8 were N-glycosylated; (iv) gM8 formed a specific complex with gN8; and (v) gN8 was required for functional processing of gM8. Co-expression of gM8 and gN8 inhibited cell fusion induced either by a combination of herpes simplex virus type 1 glycoproteins or by Molony murine leukaemia virus envelope protein. These results indicate that, in addition to the similar biochemical properties, the fusion inhibition reported previously only for alphaherpesviruses is a function conserved in the gammaherpesvirus subfamily.

Molecular characterization of strains of Human herpesvirus 8 from Japan, Argentina and Kuwait.

Current genotyping systems for Human herpesvirus 8 (HHV-8) are based on the highly variable gene encoding the K1 glycoprotein. Most strains collected worldwide cluster into two subtypes (I/A and II/C). Sequenced African strains have belonged to subtypes I/A and IV/B. Members of all three of these subtypes can have either the M or P allele at the right-hand side (RHS) of the genome. Strains obtained predominantly from aboriginal or relatively isolated populations have formed clades that branch at a distance from subtypes I/A and II/C, all being of the RHS P allele. The characterization is reported here of 16 Japanese, two Kuwaiti and five Argentine HHV-8 strains obtained from human immunodeficiency virus-infected and non-infected patients with Kaposi's sarcoma (KS), primary effusion lymphoma, multicentric Castleman's disease or renal transplants. K1 sequences of five Japanese, one Kuwaiti and two Argentine strains were identified as subtype I/A and eight Japanese, one Kuwaiti and three Argentine strains were subtype II/C. Three strains from elderly classic KS patients originally from Hokkaido, a northern Japanese island, were relatively closely related to strains of subtypes III/D and E. Consistent with previous observations, both the M and P alleles were identified at the RHS of subgroup I/A and II/C genomes; only the P allele was detected among the three Hokkaido strains. Distances among the Hokkaido strains were similar to the distance between subtypes I/A and II/C, suggesting that the Hokkaido strains may represent two distinct subtypes and that, as more strains are analysed, the currently recognized III/D subgroups will probably emerge as independent subtypes.