An early event in the herpes simplex virus type-2 replication cycle is sufficient to induce Chlamydia trachomatis persistence

Abstract

SummaryEpidemiological studies have demonstrated that co-infections of herpes simplex virus type 2 (HSV-2) and Chlamydia trachomatis occur in vivo. Data from a tissue culture model of C. trachomatis/HSV-2 co-infection indicate that viral co-infection stimulates the formation of persistent chlamydiae. Transmission electron microscopic (TEM) analyses demonstrated that in both HeLa and HEC-1B cells, co-infection caused developing chlamydiae to exhibit swollen, aberrantly shaped reticulate bodies (RBs), characteristically observed in persistence. Additionally, HSV-2 co-infection suppressed production of infectious chlamydial elementary bodies (EBs) in both host cell types. Co-infection with HSV type 1 (HSV-1) produced similar morphologic alterations and abrogated infectious EB production. These data indicate that virusinduced chlamydial persistence was neither host cellnor virus strain-specific. Purification of crude HSV-2 stocks demonstrated that viral particles were required for coinfection-induced chlamydial persistence to occur. Finally, co-infection with either UV-inactivated, replication-incompetent virus or replication-competent HSV-2 in the presence of cyclohexamide reduced chlamydial infectivity without altering chlamydial genomic DNA accumulation. These data demonstrate that productive viral replication is not required for the induction of chlamydial persistence and suggest that HSV attachment and entry can provide the necessary stimulus to alter C. trachomatis development.

Comparison of Chlamydia trachomatis serovar L2 growth in polarized genital epithelial cells grown in three-dimensional culture with non-polarized cells

“…Interestingly, when serovar E was grown in similar conditions and analyzed with the same approach, initial EB-to-RB differentiation was found to occur earlier in endometrial HEC-1B cells compared to endocervical HeLa cells, and higher chlamydial genome and transcript numbers were detected throughout the developmental cycle in the former cell line [13]; these differences were in fact the result of a faster growth of this urogenital strain in the HEC-1B cells, leading to the recovery of ca. 4-10 times more chlamydial progeny compared to HeLa cells [13,14]. Thus, while physiological differences between endometrial and endocervical cells appear to greatly influence the growth of urogenital serovar E, the more invasive serovar L2 grows equally well in both environments.…”

“…Of note, infectious titers obtained by these authors for genital serovar L2 in conjunctival cells were lower than those in endocervical HeLa cells, although the drop in infectivity was not nearly as dramatic as that for serovar D. Also, very recently, using polarized genital epithelial cells grown in 3D bead cultures, our group found that C. trachomatis serovar E grows faster in endometrial HEC-1B than in endocervical HeLa cells, which resulted in the recovery of ca. 4 times more chlamydial progeny in the former cell line upon completion of the developmental cycle [13]; other authors reported a 10-fold difference in the number of serovar E infectious progeny recovered between these two cell lines [14]. These differences in recoverable bacterial yields are potentially important, as collecting sufficient numbers of chlamydiae for downstream applications can sometimes be challenging and time-consuming, particularly when studying urogenital strains.…”

Herpes simplex virus co-infection-induced Chlamydia trachomatis persistence is not mediated by any known persistence inducer or anti-chlamydial pathway

“…trachomatis coinfections have indicated that HSV-2 co-infection alters chlamydial development; however, previous studies did not examine the co-infection process in detail (Chiarini et al, 1996;Pontefract et al, 1989;Superti et al, 2001). Data from a tissue culture model of C. trachomatis and HSV-2 co-infection established in our laboratory indicate that, during C. trachomatis serovar E and HSV-2 co-infection, HSV attachment and/or entry transmits a signal which interrupts the normal chlamydial developmental cycle and induces persistence (Deka et al, 2007). These and other data have led us to hypothesize that HSV attachment to and/or entry activates a novel anti-chlamydial defence pathway in mucosal epithelial cells.…”

Antiviral responses of human Fallopian tube epithelial cells to toll-like receptor 3 agonist poly(I:C)

“…It is well documented that infection with one pathogen can alter the risks of infection with a second pathogen. For example, a recent study has shown that Herpes simplex virus 2 can induce persistence of Chlamydia trachomatis in human female reproductive tract epithelial cells (57).. To determine whether stimulation of FTEC with TLR3 agonist results in the upregulation of other TLR, we exposed FTEC to apical treatments of poly (I:C) for 24 h and prior to measuring the levels of mRNA expression for TLR2, 3, 4, 5, 7, and 9 by real-time RT-PCR. As shown in Figure 6, poly(I:C) treatment resulted in a significant upregulation of TLR2, 3, and 7.…”