A Systematic Analysis of Host Factors Reveals a Med23-Interferon-? Regulatory Axis against Herpes Simplex Virus Type 1 Replication

Griffiths, Samantha J.; Koegl, Manfred; Boutell, Chris; Zenner, Helen L.; Crump, Colin M.; Pica, Francesca; Gonzalez, Orland; Friedel, Caroline C.; Barry, Gerald; Martin, Kim; Craigon, Marie H.; Chen, Rui; Kaza, Lakshmi N.; Fossum, Even; Fazakerley, John K.; Efstathiou, Stacey; Volpi, Antonio; Zimmer, Ralf; Ghazal, Peter; Haas, Jürgen

To determine if the clinical severity of HSV-1 disease is due to the observed deficiency in IFN-l expression, we screened a subset of the recurrent herpes labialis (HL) cohort and additional subjects for the IFN-l3 promoter polymorphism. Genotypic analysis found the presence of a T (CT or TT genotype) had a dose-dependent association with clinical severity, with the homozygous TT genotype being more prevalent as disease severity increases ( Figure 6 ). In spite of the relatively small sample numbers in some clinical categories (Table 1) , the association of a CT or TT genotype with the most severe recurrence of herpes labialis (H+) was statistically significant (p = 0.014; Fishers's exact t-test). As the CC genotype is directly associated with increased IFN-l3 levels [51] , these data highlight a previously unknown association between the frequency/severity of recurrence of herpes labialis, the CT/TT genotype and subsequent reduction in secretion of IFN-l3. It is of importance to investigate this genotype association with a larger cohort of HL patients, as well as those suffering with other HSV-1-related disease, in order to determine the role of IFN-l in the full spectrum of HSV-1 pathogenesis.