Abstract
Over the last two decades many host cell proteins have been described to be involved in the process of infectious entry of oncogenic human papillomaviruses (HPV). After initial binding and priming of the capsid, a sequence of events on the cell surface precedes the formation of the HPV entry platform. It has been shown that the virus-associated entry complex consists of membrane organizers, tetraspanins CD151 and CD63, and their associated partner proteins such as integrins, growth factor receptors, and the annexin A2 heterotetramer. Further recruitment of cytoplasmic factors such as the obscurin-like protein 1 and actin results in a non-canonical clathrin-independent endocytosis of the virus. Internalized viruses are then routed to multivesicular bodies for capsid disassembly. This early trafficking again involves annexins, and tetraspanin proteins. In this review, we summarize the current knowledge about HPV16 endocytosis and the subsequent endosomal trafficking. Moreover, we propose a model on how tetraspanins and annexins organize the spatial accumulation of HPV16-associated molecules, the recruitment of cytoplasmic trafficking factors, and the L2 membrane penetration to trigger virus entry.
Highlights
Over the last two decades many host cell proteins have been described to be involved in the process of infectious entry of oncogenic human papillomaviruses (HPV)
A number of studies revealed the involvement of distinct cellular proteins as secondary HPV16binding partners: laminin-binding integrin complexes [1,2], growth factor receptors (GFR) [3,4], the phospholipid-binding protein annexin A2 [4,5], and tetraspanins [2,6,7]
Further investigations revealed that HPV16 endocytosis depends on the tetraspanin CD151 [2,6], the cytoskeletal adaptor obscurin-like 1 (OBSL1) [11], and the phospholipid-binding protein annexin A2 [4,5]
Summary
Oncogenic human papillomaviruses (HPV) of the genus alpha, such as HPV16, HPV18, and HPV31, enter keratinocytes via a pathway that depends on a coordinated sequence of events. It includes wounding of the mucosa, virus attachment to the extracellular matrix, followed by binding to primary and secondary receptor complexes, modifications of L1 and L2 capsid proteins and cell surface components as well as triggering signaling cascades These extracellular events lead to the association of the viral capsid with the entry receptor complex (Fig. 1). Whether the secondary entry complex harbors additional HPV16 entry components remains to be determined
Sign-in/Register to view highlights & summary 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.
