Inter- and intragenic variations complicate the molecular epidemiology of human cytomegalovirus.
Human cytomegalovirus isolates were analyzed, both by restriction fragment-length polymorphism typing and by sequencing for intra- and intergenic variability at 9 sites on the genome, to determine whether genetic variation influenced disease outcome and whether linkage among genes could be identified. Variation at the UL55 (glycoprotein B [gB]), UL74 (gO), UL75 (gH), UL115 (gL), US9, and US28 gene open-reading frames was studied in relationship to outcome of cytomegalovirus disease. Major findings were that (1) on the basis of analysis of only 9 genomic sites, it is apparent that an almost infinite number of genetic combinations are theoretically possible; (2) genetic linkages are rare; (3) intragenic variability may be a complicating factor in molecular epidemiologic studies; and (4) analysis of only a single gene from a clinical isolate may not reveal the presence of either intragenic variants or mixtures of genotypes.
Rasmussen
Lucy
L
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Center for AIDS Research, Stanford University School of Medicine, Stanford, CA 94305, USA. lucyrasmussen@stanford.edu
Geissler
Aimee
A
Winters
Mark
M
D003587:Cytomegalovirus / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000821:virology; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008562:Membrane Glycoproteins / Q000235:genetics; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D019707:Receptors, Chemokine / Q000235:genetics; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
D008562:Membrane Glycoproteins; D019707:Receptors, Chemokine; C456063:US9 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C040495:glycoprotein B, Simplexvirus