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bioRxiv · 10.1101/2024.09.27.615334

TvAP65 in Trichomonas vaginalis Promotes HPV Infection by Interacting with Host Molecules

Mei, X.·Sheng, W.·Zhang, Y.·Tian, W.·Tian, X.·Yang, Z.·Wang, S.·Zhang, Z.
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Abstract

Cervical cancer induced by human papillomavirus (HPV) infection poses a serious threat to womens health. Studies have shown that Trichomonas vaginalis (T. vaginalis), which is widely prevalent globally, can facilitate HPV infection. However, the underlying mechanism remains unclear. This study found that T. vaginalis significantly enhanced HPV infection in HaCaT cells and mouse vaginas through in vivo and in vitro experiments, and promoted the expression of HPV membrane receptor molecules CD151 and HSPG2. The HPV infection rate and CD151/HSPG2 expression levels were significantly decreased after reducing the expression of T. vaginalis adhesion protein 65 (TvAP65). In contrast, both HPV infection rates and CD151/HSPG2 expression were significantly increased in HaCaT cells over-expressing TvAP65. When both TvAP65 in T. vaginalis and CD151/HSPG2 in HaCaT cells were knocked down simultaneously, the infection rate of HPV in HaCaT cells was further reduced. These results suggest that TvAP65 promotes HPV infection by up-regulating the expression of CD151 and HSPG2. Furthermore, this study knocked down the 12 interacting molecules of TvAP65 in HaCaT cells one by one, and found that the HPV infection rate was significantly reduced after T. vaginalis infected HaCaT cells with low expression of FTH1, SPCS1, ATP5MC3, ITGB7, PMEPA1 or REEP5. Among them, SPCS1 played the most significant role. Simultaneous knockdown of TvAP65 and SPCS1 further significantly down-regulated the infection rate of HPV in HaCaT cells. Moreover, this molecule also down-regulated the promoting effect of T. vaginalis on HSPG2/CD151 expression. These results imply that SPCS1 plays an important role in T. vaginalis promoting HSPG2/CD151 expression and HPV infection. This study not only further proved that T. vaginalis can promote HPV infection but also explores the molecular mechanism by which TvAP65, through its interaction with SPCS1, up-regulates the expression of HSPG2 and CD151, thereby facilitating HPV infection. This provides a theoretical basis for clarifying the mechanism of co-infection between T. vaginalis and HPV.

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Mei, X., Sheng, W., Zhang, Y., Tian, W., Tian, X., Yang, Z., Wang, S., Zhang, Z.. 2024-09-27. TvAP65 in Trichomonas vaginalis Promotes HPV Infection by Interacting with Host Molecules. https://doi.org/10.1101/2024.09.27.615334

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