Abstract
Human papillomavirus (HPV) is the most common sexually transmitted pathogen in the United States, causing 99% of cervical cancers and 5% of all human cancers worldwide. HPV infection requires transport of the viral genome (vDNA) into the nucleus of basal keratinocytes. During this process, minor capsid protein L2 facilitates subcellular retrograde trafficking of the vDNA from endosomes to the Golgi, and accumulation at host chromosomes during mitosis for nuclear retention and localization during interphase. Here we investigated the relationship between cellular glutathione (GSH) and HPV16 infection. siRNA knockdown of GSH biosynthetic enzymes results in a partial decrease of HPV16 infection. Likewise, infection of HPV16 in GSH depleted keratinocytes is inefficient, an effect that was not seen with adenoviral vectors. Analysis of trafficking revealed no defects in cellular binding, entry, furin cleavage of L2, or retrograde trafficking of HPV16, but GSH depletion hindered post-Golgi trafficking and translocation, decreasing nuclear accumulation of vDNA. Although precise mechanisms have yet to be defined, this work suggests that GSH is required for a specific post-Golgi trafficking step in HPV16 infection.
Highlights
Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States [1]
We find that siRNA knockdown of key enzymes in the GSH synthesis pathway impairs HPV16 pseudovirus infection
GSH is important for HPV infection synthetase (GSS, EC 6.3.2.3) adds glycine to γ-GC, forming GSH [48]
Summary
Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States [1]. There are >400 HPV types that have been deposited and annotated in the Papillomavirus Episteme (PAVE) database [2]. Clinically relevant HPV can be divided into low-risk HPV, causing cutaneous and mucosal warts, and cancer-associated high-risk HPV [3,4]. High-risk HPV are associated with 99% of cervical cancers and 5% of all human cancers worldwide [5,6]. HPV16 belongs to the high-risk HPV, and HPV16 alone is responsible for >50% cervical cancers [7]. There are highly effective vaccines being used to prevent high-risk HPV infection, but the vaccine cannot protect against all types of high-risk HPV infection and the high cost prevents people from developing world to get access to the vaccine [7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
