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Human papillomaviruses: diversity, infection and host interactions

Abstract

Human papillomaviruses (HPVs) are an ancient and highly successful group of viruses that have co-evolved with their host to replicate in specific anatomical niches of the stratified epithelia. They replicate persistently in dividing cells, hijack key host cellular processes to manipulate the cellular environment and escape immune detection, and produce virions in terminally differentiated cells that are shed from the host. Some HPVs cause benign, proliferative lesions on the skin and mucosa, and others are associated with the development of cancer. However, most HPVs cause infections that are asymptomatic and inapparent unless the immune system becomes compromised. To date, the genomes of almost 450 distinct HPV types have been isolated and sequenced. In this Review, I explore the diversity, evolution, infectious cycle, host interactions and disease association of HPVs.

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Fig. 1: Phylogenetic tree of human papillomaviruses.
Fig. 2: Human papillomavirus infectious cycles in stratified epithelia of different host tissues.
Fig. 3: Genomic organization of human papillomaviruses from different genera.
Fig. 4: Natural course of infection by different human papillomaviruses.
Fig. 5: Mechanisms of carcinogenesis.

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Acknowledgements

Work in the author’s laboratory is funded by the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases (NIAID) (grant number ZIA1000713). The author thanks R. Kissinger (NIAID) for drawing a draft for Fig. 2.

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Related links

International Agency for Research on Cancer: https://www.iarc.who.int

International Committee on Taxonomy of Viruses: https://talk.ictvonline.org

International HPV Reference Center: https://ki.se/en/labmed/international-hpv-reference-center

Papillomavirus Episteme: https://pave.niaid.nih.gov

Glossary

Cutaneous epithelium

Layers of stratified keratinocytes that form the outer layer of the skin.

Mucosal epithelium

The moist mucous epithelium that is present at the entrance to body cavities.

Oncogenic HPV types

‘High-risk’ human papillomavirus (HPV) types that are associated with the development of several human cancers.

p53

A tumour suppressor protein that restricts cell growth when cells are damaged; p53 is very often mutated in non-human papillomavirus (non-HPV) cancers.

PDZ-binding domain

The complementary recognition module of PDZ domains, which are interaction modules found in many proteins.

Persistent infection

A long-term viral infection that maintains a reservoir of host cells containing the viral genome, evades immune clearance and often produces virus particles.

Keratinocyte

An epithelial cell of the epidermis that produces keratin.

Basement membrane

A thin, non-cellular layer that lies between the dermis and the epidermis of the skin.

Transformation zone

The junction between squamous and columnar epithelial cells in the cervix, anus and similar tissues. Also known as the squamocolumnar junction or transition zone.

Columnar epithelium

A single-layer, glandular epithelium that lines the endocervix.

Latency

The viral genome is dormant in cells and does not produce virus.

Retromer complex

A protein complex that sorts and traffics proteins between the endosome and trans-Golgi network.

PML nuclear bodies

Small, interferon-inducible nuclear bodies involved in many cell processes; they consist of a scaffold of PML protein but contain many other proteins.

Oncoproteins

Proteins that dysregulate the host cell, and by doing so promote carcinogenesis.

Minichromosomes

Small circular DNA molecules that are assembled in chromatin.

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McBride, A.A. Human papillomaviruses: diversity, infection and host interactions. Nat Rev Microbiol (2021). https://doi.org/10.1038/s41579-021-00617-5

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