Sequence variation in the herpes simplex virus U(S)1 ocular virulence determinant

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• Herpes simplex virus type 1 (HSV-1) is a significant human pathogen.
• The U(S)1 gene in HSV-1 is known to influence host range and ocular virulence.
• Previous studies identified virulence-affecting mutations in specific strains, but comprehensive genomic variation data was lacking.

Purpose of the Study:

• To investigate the sequence variation of the HSV-1 U(S)1 gene across multiple ocular isolates.
• To identify conserved regions and potential functional motifs within the U(S)1 protein.

Main Methods:

• Sequencing of the U(S)1 gene from six ocular HSV-1 isolates and two reference strains (KOS and F).
• Application of bioinformatics analyses, including MEME, to analyze sequence data.

Main Results:

• Identical amino acid sequences were observed in strains 17, F, CJ394, and CJ311.
• Most sequence variability was concentrated in the amino-terminal third of the U(S)1 protein.
• A conserved 63-residue core sequence (motif 1) was identified in all analyzed alpha-herpesvirus U(S)1 homologs, located within a structured region. Ten absolutely conserved amino acids were found in this central core. Consensus-binding motifs for host proteins were also detected.

Conclusions:

• Significant sequence variation exists within the HSV-1 U(S)1 gene.
• The alpha22 protein features a conserved central core and variable amino/carboxyl termini.
• Ten amino acids are conserved across alpha-herpesvirus U(S)1 homologs, suggesting critical functional roles.
• Potential interactions between HSV-1 U(S)1/U(S)1.5 proteins and host factors were indicated, guiding future research on structure-function relationships and pathogenesis.