IDENTIFICATION OF THE GENE ENCODING THE MAJOR LATENCY-ASSOCIATED NUCLEAR ANTIGEN OF THE KAPOSIS SARCOMA-ASSOCIATED HERPESVIRUS

Over 85% of patients with Kaposi's sarcoma (KS) are seropositive for a ntibodies to the latency-associated nuclear antigen (LANA) expressed i n B cell lines infected with Kaposi's sarcoma-associated herpesvirus ( KSHV), The presence of antibodies to LANA strongly correlates with the risk of developing the disease, However, the identity of the protein( s) comprising LANA and the corresponding gene(s) has remained unclear, To identify potential latent gene candidates for LANA, we probed tota l RNA extracted from BCBL-1 cells (a B cell line latently infected wit h KSHV) using lambda clones that span the KSHV genome, One region enco ding latent transcripts spanned KSHV open reading frames (orfs) 71 (K1 3), 72 (v-cyclin), and 73, Among these, however, only orf 73, when exp ressed in heterologous mammalian cell systems, reacted with KSHV antib ody-positive human sera, resulting in a punctate nuclear staining patt ern reminiscent of LANA in BCBL-1 cells, Furthermore, extracts from ce lls expressing the orf 73 protein product specifically blocked the bin ding of KS patient antibodies to LANA. Finally, seroreactivity with re combinant orf 73 protein exactly paralleled reactivity with classical LANA as expressed in BCBL-1 cells, both in KS patients and in other gr oups, Together, these data support the identification of KSHV orf 73 a s the gene encoding the dominant immunogenic component of LANA.