Molecular polymorphism of Kaposi's sarcoma-associated herpesvirus (Human herpesvirus 8) latent nuclear antigen: evidence for a large repertoire of viral genotypes and dual infection with different viral genotypes.

Molecular polymorphism was found in Kaposi's sarcoma-associated herpesvirus (KSHV) latent nuclear antigen (LNA), mapped to the internal repeat domain of the encoding orf73 gene, and used to develop a novel genotyping technique, KSHV LNA genotyping (KVNAtyping). KVNAtype was stable during latent and lytic viral replication in cell culture and in humans. Diverse KVNAtypes were identified in 43 specimens: 6 KSHV cell lines and 6 Kaposi's sarcoma (KS) and 4 primary effusion lymphoma (PEL) tumor samples from the United States, 15 KS tumor samples from Italy, and 12 KS tumor samples from Zambia. A single KVNAtype was detected in each of 41 specimens, and 2 KVNAtypes were detected in each of 2 KS specimens. Multifocal KS from 3 patients showed the same single KVNAtype at all sites in each patient. These results demonstrate a large repertoire of KSHV genotypes and suggest that the development of most KSs and PELs is associated with a single viral genotype.