HHV-8/KSHV proteins involved in signaling and transformation

When the first partial and complete sequences of Kaposis sarcoma herpesviruswere obtained (Neipel et al. 1997; Nicholas et al. 1997; Russo et al. 1996), itbecame apparent that the presence of multiple viral genes with low but significanthomologies to mammalian proteins involved in signal transduction is oneof the key features of this virus. While equivalents of some of these homologueshad been found in other herpesviruses or other large DNA viruses, for examplechemokines and chemokine receptors, others such as interleukin-6 had notpreviously been identified in a virus. Given the low sequence homology totheir cellular counterparts and the fact that some of the cellular gene homologuesoccur in different large DNA viruses, it seems that such homologueshave entered their respective viral genomes a long time ago in the early phases ofDNA virus evolution. Their continued presence, however, points to a selectiveadvantage during virus evolution, probably by facilitating the spread andpersistence of these viruses in their hosts and by counteracting the hosts defensemechanisms. In the context of HHV-8/KSHV, a particularly interesting questionis whether some of these homologues, and other viral proteins capable ofactivating intracellular signaling pathways, may contribute to oncogenesis.This review discusses the evidence available for individual HHV-8/KSHVgenes.