Interferon lambda 4 genotype is not associated with recurrence of oral or genital herpes

Krystle A Lang Kuhs, Mark H. Kuniholm, Ruth M. Pfeiffer, Sabrina Chen, Seema Desai, Brian R. Edlin, Marion G. Peters, Michael Plankey, Gerald B. Sharp, Howard Strickler, Maria C. Villacres, Thomas C. Quinn, Stephen J. Gange, Ludmila Prokunina-Olsson, Ruth M. Greenblatt, Thomas R. O'Brien

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

IFNL4-δG/TT (rs368234815) genotype is associated with hepatitis C virus clearance and may play a role in other infections. IFN-ë4 protein is generated only in individuals who carry the IFNL4-δG allele. The IFNL4 rs12979860-T allele, which is in strong linkage disequilibrium with IFNL4-δG, was recently reported to be associated with more frequent and severe oral herpes episodes. We investigated the association of IFNL4-δG/TT with herpes simplex virus (HSV)-related outcomes among 2,192 African American and European American participants in the Women's Interagency HIV Study (WIHS). WIHS is a prospective cohort study of human immunodeficiency virus (HIV)'infected and at-risk women that began in 1994. This report includes follow-up through 2013. Available data included: HSV'1 and HSV'2 antibodies at study entry; bi-annually ascertained episodes of (self-reported) oral herpes, (self-reported) genital sores and (clinician-observed) genital ulcers; HSV'2 DNA in cervicovaginal lavage (CVL) specimens. IFNL4-δG/TT genotyping was determined by Taq- Man. We compared women with IFNL4-δG/δG or IFNL4-TT/δG genotypes (i.e., IFNL4-δG carriers) to those with the IFNL4-TT/TT genotype, adjusting for age, race and HIV status. For outcomes with repeated measurements, the adjusted odds ratio (aOR), 95% confidence interval [CI] and p-value were determined using a generalized estimating equations approach. Median participant age at enrollment was 36 years; 81% were African American, 74% were HIV-infected. Among 1,431 participants tested for antibodies, 72.8%were positive for HSV'1 and 79.0% were positive for HSV'2. We observed no association between IFNL4-δG/TT genotype and any outcome: HSV'1 or HSV'2 antibody prevalence (p>0.1, all comparisons); oral herpes (aOR, 1.2; p = 0.35); genital sores (aOR, 1.0; p = 0.71); genital ulcers (aOR, 1.1; p = 0.53); detectable HSV'2 DNA in CVL (N = 322; aOR, 0.71; p = 0.49); HSV'2 DNA level (p = 0.68). In this large prospective study, IFNL4-δG/TT genotype was not associated with HSV-related outcomes, including episodes of oral or genital herpes.

Original languageEnglish (US)
Article numbere0138827
JournalPLoS One
Volume10
Issue number10
DOIs
StatePublished - Oct 2 2015

Fingerprint

Human herpesvirus 2
Herpes Genitalis
Human Herpesvirus 2
interferons
Viruses
Interferons
genitalia
mouth
odds ratio
Genotype
Human immunodeficiency virus
Human herpesvirus 1
Recurrence
Odds Ratio
HIV
genotype
Human Herpesvirus 1
herpes simplex
Therapeutic Irrigation
Simplexvirus

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Kuhs, K. A. L., Kuniholm, M. H., Pfeiffer, R. M., Chen, S., Desai, S., Edlin, B. R., ... O'Brien, T. R. (2015). Interferon lambda 4 genotype is not associated with recurrence of oral or genital herpes. PLoS One, 10(10), [e0138827]. https://doi.org/10.1371/journal.pone.0138827

Interferon lambda 4 genotype is not associated with recurrence of oral or genital herpes. / Kuhs, Krystle A Lang; Kuniholm, Mark H.; Pfeiffer, Ruth M.; Chen, Sabrina; Desai, Seema; Edlin, Brian R.; Peters, Marion G.; Plankey, Michael; Sharp, Gerald B.; Strickler, Howard; Villacres, Maria C.; Quinn, Thomas C.; Gange, Stephen J.; Prokunina-Olsson, Ludmila; Greenblatt, Ruth M.; O'Brien, Thomas R.

In: PLoS One, Vol. 10, No. 10, e0138827, 02.10.2015.

Research output: Contribution to journalArticle

Kuhs, KAL, Kuniholm, MH, Pfeiffer, RM, Chen, S, Desai, S, Edlin, BR, Peters, MG, Plankey, M, Sharp, GB, Strickler, H, Villacres, MC, Quinn, TC, Gange, SJ, Prokunina-Olsson, L, Greenblatt, RM & O'Brien, TR 2015, 'Interferon lambda 4 genotype is not associated with recurrence of oral or genital herpes', PLoS One, vol. 10, no. 10, e0138827. https://doi.org/10.1371/journal.pone.0138827
Kuhs KAL, Kuniholm MH, Pfeiffer RM, Chen S, Desai S, Edlin BR et al. Interferon lambda 4 genotype is not associated with recurrence of oral or genital herpes. PLoS One. 2015 Oct 2;10(10). e0138827. https://doi.org/10.1371/journal.pone.0138827
Kuhs, Krystle A Lang ; Kuniholm, Mark H. ; Pfeiffer, Ruth M. ; Chen, Sabrina ; Desai, Seema ; Edlin, Brian R. ; Peters, Marion G. ; Plankey, Michael ; Sharp, Gerald B. ; Strickler, Howard ; Villacres, Maria C. ; Quinn, Thomas C. ; Gange, Stephen J. ; Prokunina-Olsson, Ludmila ; Greenblatt, Ruth M. ; O'Brien, Thomas R. / Interferon lambda 4 genotype is not associated with recurrence of oral or genital herpes. In: PLoS One. 2015 ; Vol. 10, No. 10.
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abstract = "IFNL4-δG/TT (rs368234815) genotype is associated with hepatitis C virus clearance and may play a role in other infections. IFN-{\"e}4 protein is generated only in individuals who carry the IFNL4-δG allele. The IFNL4 rs12979860-T allele, which is in strong linkage disequilibrium with IFNL4-δG, was recently reported to be associated with more frequent and severe oral herpes episodes. We investigated the association of IFNL4-δG/TT with herpes simplex virus (HSV)-related outcomes among 2,192 African American and European American participants in the Women's Interagency HIV Study (WIHS). WIHS is a prospective cohort study of human immunodeficiency virus (HIV)'infected and at-risk women that began in 1994. This report includes follow-up through 2013. Available data included: HSV'1 and HSV'2 antibodies at study entry; bi-annually ascertained episodes of (self-reported) oral herpes, (self-reported) genital sores and (clinician-observed) genital ulcers; HSV'2 DNA in cervicovaginal lavage (CVL) specimens. IFNL4-δG/TT genotyping was determined by Taq- Man. We compared women with IFNL4-δG/δG or IFNL4-TT/δG genotypes (i.e., IFNL4-δG carriers) to those with the IFNL4-TT/TT genotype, adjusting for age, race and HIV status. For outcomes with repeated measurements, the adjusted odds ratio (aOR), 95{\%} confidence interval [CI] and p-value were determined using a generalized estimating equations approach. Median participant age at enrollment was 36 years; 81{\%} were African American, 74{\%} were HIV-infected. Among 1,431 participants tested for antibodies, 72.8{\%}were positive for HSV'1 and 79.0{\%} were positive for HSV'2. We observed no association between IFNL4-δG/TT genotype and any outcome: HSV'1 or HSV'2 antibody prevalence (p>0.1, all comparisons); oral herpes (aOR, 1.2; p = 0.35); genital sores (aOR, 1.0; p = 0.71); genital ulcers (aOR, 1.1; p = 0.53); detectable HSV'2 DNA in CVL (N = 322; aOR, 0.71; p = 0.49); HSV'2 DNA level (p = 0.68). In this large prospective study, IFNL4-δG/TT genotype was not associated with HSV-related outcomes, including episodes of oral or genital herpes.",
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AU - Kuhs, Krystle A Lang

AU - Kuniholm, Mark H.

AU - Pfeiffer, Ruth M.

AU - Chen, Sabrina

AU - Desai, Seema

AU - Edlin, Brian R.

AU - Peters, Marion G.

AU - Plankey, Michael

AU - Sharp, Gerald B.

AU - Strickler, Howard

AU - Villacres, Maria C.

AU - Quinn, Thomas C.

AU - Gange, Stephen J.

AU - Prokunina-Olsson, Ludmila

AU - Greenblatt, Ruth M.

AU - O'Brien, Thomas R.

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N2 - IFNL4-δG/TT (rs368234815) genotype is associated with hepatitis C virus clearance and may play a role in other infections. IFN-ë4 protein is generated only in individuals who carry the IFNL4-δG allele. The IFNL4 rs12979860-T allele, which is in strong linkage disequilibrium with IFNL4-δG, was recently reported to be associated with more frequent and severe oral herpes episodes. We investigated the association of IFNL4-δG/TT with herpes simplex virus (HSV)-related outcomes among 2,192 African American and European American participants in the Women's Interagency HIV Study (WIHS). WIHS is a prospective cohort study of human immunodeficiency virus (HIV)'infected and at-risk women that began in 1994. This report includes follow-up through 2013. Available data included: HSV'1 and HSV'2 antibodies at study entry; bi-annually ascertained episodes of (self-reported) oral herpes, (self-reported) genital sores and (clinician-observed) genital ulcers; HSV'2 DNA in cervicovaginal lavage (CVL) specimens. IFNL4-δG/TT genotyping was determined by Taq- Man. We compared women with IFNL4-δG/δG or IFNL4-TT/δG genotypes (i.e., IFNL4-δG carriers) to those with the IFNL4-TT/TT genotype, adjusting for age, race and HIV status. For outcomes with repeated measurements, the adjusted odds ratio (aOR), 95% confidence interval [CI] and p-value were determined using a generalized estimating equations approach. Median participant age at enrollment was 36 years; 81% were African American, 74% were HIV-infected. Among 1,431 participants tested for antibodies, 72.8%were positive for HSV'1 and 79.0% were positive for HSV'2. We observed no association between IFNL4-δG/TT genotype and any outcome: HSV'1 or HSV'2 antibody prevalence (p>0.1, all comparisons); oral herpes (aOR, 1.2; p = 0.35); genital sores (aOR, 1.0; p = 0.71); genital ulcers (aOR, 1.1; p = 0.53); detectable HSV'2 DNA in CVL (N = 322; aOR, 0.71; p = 0.49); HSV'2 DNA level (p = 0.68). In this large prospective study, IFNL4-δG/TT genotype was not associated with HSV-related outcomes, including episodes of oral or genital herpes.

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