title: Chlamydial Pre-Infection Protects from Subsequent Herpes Simplex Virus-2 Challenge in a Murine Vaginal Super-Infection Model.
abstract: Chlamydia trachomatis and Herpes Simplex Virus-2 (HSV-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. Limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. To determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infected animals, we developed an in vivo super-infection model in which female BALB/c mice were vaginally infected with Chlamydia muridarum (Cm) followed later by HSV-2. Pre-infection with Chlamydia 3 or 9 days prior to HSV-2 super-infection conferred significant protection from HSV-2-induced neurologic disease and significantly reduced viral recovery compared to HSV-2 singly-infected controls. Neither protection from mortality nor reduced viral recovery were observed when mice were i) super-infected with HSV-2 on day 27 post Cm; ii) infected with UV-irradiated Cm and super-infected with HSV-2; or iii) azithromycin-treated prior to HSV-2 super-infection. Therefore, protection from HSV-2-induced disease requires active infection with viable chlamydiae and is not observed after chlamydial shedding ceases, either naturally or due to antibiotic treatment. Thus, Chlamydia-induced protection is transient and requires the continued presence of chlamydiae or their components. These data demonstrate that chlamydial pre-infection can alter progression of subsequent HSV-2 infection, with implications for HSV-2 transmission from co-infected humans.
authors.affiliation: Department of Biomedical Sciences, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Slade
authors.affiliation: Department of Biomedical Sciences, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Jennifer V
authors.initials: JV
authors.lastname: Hall
authors.affiliation: Department of Biomedical Sciences, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kintner
authors.affiliation: Department of Biomedical Sciences, Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Schoborg
mesh_terms: D000818:Animals; D017963:Azithromycin / Q000627:therapeutic use; D002690:Chlamydia Infections / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology / Q000821:virology; D002692:Chlamydia trachomatis / Q000302:isolation & purification / Q000502:physiology* / Q000528:radiation effects; D060085:Coinfection; D018450:Disease Progression; D005260:Female; D006558:Herpes Genitalis / Q000150:complications / Q000382:microbiology / Q000517:prevention & control* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000302:isolation & purification / Q000502:physiology*; D054884:Host-Pathogen Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D010264:Paraplegia / Q000209:etiology / Q000821:virology; D015163:Superinfection; D013997:Time Factors; D016585:Vaginosis, Bacterial / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology / Q000821:virology; D019562:Viral Load
chemical_list: D017963:Azithromycin