Human cytomegalovirus (HCMV) glycoprotein M occurs in three distinct genotypes in laboratory strains and clinical isolates.

BACKGROUND

HCMV carries virus-encoded envelope glycoproteins important for viral attachment, entry into host cells and replication. These glycoproteins have polymorphic features resulting in distinct genotypes some of which have been associated with disease outcome. Glycoprotein complex II comprises glycoproteins M (gM) and N (gN) and is essential for viral replication. Glycoprotein N is highly polymorphic while gM is highly conserved. The existence of distinct gM genotypes has not previously been reported.

STUDY

DESIGN

PCR amplification of the entire gM gene (1298 bp) was carried out on five HCMV laboratory strains (AD169, Towne, Davis, Toledo, Merlin) and ten clinical isolates. PCR product was sequenced and nucleotide and aminoacid phylogenetic trees constructed for these samples and for an additional 287 HCMV gM sequences obtained from NCBI database. The hydrophobicity of the predicted protein sequences was compared.

RESULTS

Three distinct genotypes were identified (gM1, gM2 and gM3) with every sequence aligning with one genotype, suggesting they are stable polymorphisms rather than random nucleotide substitutions. Aminoacid translation of the nucleotide sequences merged gM1 and gM2, but gM3 remained as a distinct and separate type. The aminoacid substitutions led to changes in the hydrophobicity of the 3 glycoprotein types particularly between gM3 and the other two types.

CONCLUSIONS

Glycoprotein M is highly conserved, but we have identified three distinct genotypes, arising from variability in a small region of the genome. These changes altered the predicted hydrophobicity of the glycoprotein potentially altering the conformational structure of the glycoprotein and affecting its function in vivo.