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.
Highlights
Herpes Simplex Virus Type-2 and Chlamydia trachomatis are two of the most common sexually transmitted pathogens in the world
To further dissect the interactions between host and pathogen that occur during Chlamydia and Herpes Simplex Virus-2 (HSV-2) co-infections, we developed an in vivo C. muridarum and HSV-2 murine genital tract super-infection model
To begin characterizing the disease progression of Chlamydia and HSV-2 within the co-infected host, mice were vaginally infected with 106 inclusion forming units (IFU) C. muridarum (Cm) on day 0 and super-infected with 5 x 103 PFU HSV-2 on day 3 post chlamydial infection
Summary
Herpes Simplex Virus Type-2 and Chlamydia trachomatis are two of the most common sexually transmitted pathogens in the world. More than 500 million people aged 15–49, or 16% of the population in this age range, are living with HSV-2 [1]. Chlamydia and HSV-2 Vaginal Co-Infection Mouse Model data collection and analysis, decision to publish, or preparation of the manuscript
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