Differential viral protein expression in Kaposi's sarcoma-associated herpesvirus-infected diseases - Kaposi's sarcoma, primary effusion lymphoma, andmulticentric Castleman's disease

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is Linked to KS, primar y effusion lymphomas (PEL), and a subset of multicentric Castleman's diseas e (MCD), Transcript mapping studies using PEL cell lines have allowed preli minary classification of viral gene expression into constitutive (class I) and inducible (class II/III) categories. To determine whether viral gene ex pression differs in vivo, we examined tissue sections of KSHV-infected diso rders, using specific antibodies against proteins that are representative o f the different expression classes of KSHV genes. ORF73/LANA appears to be a surrogate marker for KSHV infection because it is constitutively expresse d in vitro and in vivo in all KSHV-infected tells. Expression of vIRF1, vIL 6, and PF-8 proteins in the infected B cells of MCD lymph nodes reproduces the expression pattern observed in TPA-stimulated KSHV-infected B-cell line s. In contrast, the protein. expression of the inducible viral genes that m e tested in KS and PEL biopsies is restricted to PF-8 and vIL6, respectivel y. The tightly restricted expression of KSHV proteins in vivo differs from the dysregulated expression of inducible KSHV genes in vitro and suggests t hat viral gene expression in KSHV-infected cell lines does not accurately r eflect what occurs in diseased tissues. These differences may be related to either cell-specific or immune restriction of viral replication.