Differentiation of Human Cytomegalovirus Genotypes in Immunocompromised Patients on the Basis of UL4 Gene Polymorphisms

The variety of clinical manifestations of human cytomegalovirus infection probably results from both viral and host factors. Because genetic markers that span the viral genome are needed to identify such viral factors, polymorphisms at the UL4 gene locus were analyzed. DNA sequence analyses revealed 4 UL4-based genotypes, 2 of which were closely related but distinguishable by an uncommon polymorphism that results in overexpression of gpUL4. Similarities in the spectra of polymorphisms detected in various sets of samples reveal that all UL4 types infect a diversity of organs in different patient groups and in different geographic locales. Simultaneous infection by >1 UL4 type is common in AIDS patients. Data from sequencing analyses and from a rapid and simple UL4 typing assay did not detect linkage between UL4 and glycoprotein B types, which suggests that UL4 genotyping should be useful for studies that attempt to identify cytomegalovirus genes involved in disease pathogenesis.