TY - JOUR
T1 - The long and winding road
T2 - human papillomavirus entry and subcellular trafficking
AU - Ozbun, Michelle A.
AU - Campos, Samuel K.
N1 - Funding Information:
This work was supported by grants from the U.S. National Institutes of Health to M.A.O ( R01 CA207368 , R21 DE028652 and P30 CA118100 ) and S.K.C ( R01 GM136853 and P30 CA023074 ). We thank members of the Ozbun and Campos labs, and Professor Koenraad Van Doorslaer for valuable feedback. Special thanks to Jocelyne Mendez from BioRender for artistic assistance. We sincerely apologize to any researchers whose work was not discussed or cited due to length constraints.
Publisher Copyright:
© 2021 The Authors
PY - 2021/10
Y1 - 2021/10
N2 - Human papillomaviruses (HPVs) infect and replicate in differentiating mucosal and cutaneous epithelium. Most HPV infections are asymptomatic or cause transient benign neoplasia. However, persistent infections by oncogenic HPV types can progress to cancer. During infectious entry into host keratinocytes, HPV particles interact with many host proteins, beginning with major capsid protein L1 binding to cellular heparan sulfate and a series of enzymatic capsid modifications that promote infectious cellular entry. After utilizing the endosomal pathway to uncoat the viral genome (vDNA), the minor capsid protein L2/vDNA complex is retrograde trafficked to the Golgi, and thereafter, to the nucleus where viral transcription initiates. Post-Golgi trafficking is dependent on mitosis, with L2-dependent tethering of vDNA to mitotic chromosomes before accumulation at nuclear substructures in G1. This review summarizes the current knowledge of the HPV entry pathway, the role of cellular proteins in this process, and notes many gaps in our understanding.
AB - Human papillomaviruses (HPVs) infect and replicate in differentiating mucosal and cutaneous epithelium. Most HPV infections are asymptomatic or cause transient benign neoplasia. However, persistent infections by oncogenic HPV types can progress to cancer. During infectious entry into host keratinocytes, HPV particles interact with many host proteins, beginning with major capsid protein L1 binding to cellular heparan sulfate and a series of enzymatic capsid modifications that promote infectious cellular entry. After utilizing the endosomal pathway to uncoat the viral genome (vDNA), the minor capsid protein L2/vDNA complex is retrograde trafficked to the Golgi, and thereafter, to the nucleus where viral transcription initiates. Post-Golgi trafficking is dependent on mitosis, with L2-dependent tethering of vDNA to mitotic chromosomes before accumulation at nuclear substructures in G1. This review summarizes the current knowledge of the HPV entry pathway, the role of cellular proteins in this process, and notes many gaps in our understanding.
UR - http://www.scopus.com/inward/record.url?scp=85112544081&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85112544081&partnerID=8YFLogxK
U2 - 10.1016/j.coviro.2021.07.010
DO - 10.1016/j.coviro.2021.07.010
M3 - Review article
C2 - 34416595
AN - SCOPUS:85112544081
VL - 50
SP - 76
EP - 86
JO - Current Opinion in Virology
JF - Current Opinion in Virology
SN - 1879-6257
ER -