The sequence and antiapoptotic functional domains of the human cytomegalovirus UL37 exon 1 immediate early protein are conserved in multiple primary strains

The human cytomegalovirus UL37 exon 1 gene encodes the immediate early prot ein pUL37x1 that has antiapoptotic and regulatory activities. Deletion muta genesis analysis of the open reading frame of UL37x1 identified two domains that are necessary and sufficient for its antiapoptotic activity. These do mains are confined within the segments between amino acids 5 to 34, and 118 to 147 respectively. The first domain provides the targeting of the protei n to mitochondria. Direct PCR sequencing of UL37 exon 1 amplified from 26 p rimary strains of human cytomegalovirus demonstrated that the promoter, pol yadenylation signal. and the two segments of pUL37x1 required for its antia poptotic function were invariant in all sequenced strains and identical to those in AD169 pUL37x1. In total, UL37 exon 1 Varies between 0.0 and 1.6% a t the nucleotide level from strain AD169. Only 11 amino acids were found to vary in one or more viral strains, and these variations occurred only in t he domains of pUL37x1 dispensable for its antiapoptotic function. We infer from this remarkable conservation of pUL37x1 in primary strains that this p rotein and, probably, its antiapoptotic function are required for productiv e replication of human cytomegalovirus in humans, (C) 2001 Academic Press.