MMBR Figure table search 04
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Longworth, M. S.
Right arrow Articles by Laimins, L. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Longworth, M. S.
Right arrow Articles by Laimins, L. A.
Microbiology and Molecular Biology Reviews, June 2004, p. 362-372, Vol. 68, No. 2
1092-2172/04/$08.00+0     DOI: 10.1128/MMBR.68.2.362-372.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Pathogenesis of Human Papillomaviruses in Differentiating Epithelia

Michelle S. Longworth and Laimonis A. Laimins*

Department of Microbiology-Immunology, The Feinberg Medical School, Northwestern University, Chicago, Illinois 60611

Human papillomaviruses (HPV) are the etiological agents of cervical and other anogenital malignancies. Over 100 different types of HPVs have been identified to date, and all target epithelial tissues for infection. One-third of HPV types specifically infect the genital tract, and a subset of these are the causative agents of anogenital cancers. Other HPV types that infect the genital tract induce benign hyperproliferative lesions or genital warts. The productive life cycle of HPVs is linked to epithelial differentiation. Papillomaviruses are thought to infect cells in the basal layer of stratified epithelia and establish their genomes as multicopy nuclear episomes. In these cells, viral DNA is replicated along with cellular chromosomes. Following cell division, one of the daughter cells migrates away from the basal layer and undergoes differentiation. In highly differentiated suprabasal cells, vegetative viral replication and late-gene expression are activated, resulting in the generation of progeny virions. Since virion production is restricted to differentiated cells, infected basal cells can persist for up to several decades or until the immune system clears the infection. The E6 and E7 genes encode viral oncoproteins that target Rb and p53, respectively. During the viral life cycle, these proteins facilitate stable maintenance of episomes and stimulate differentiated cells to reenter the S phase. The E1 and E2 proteins act as origin recognition factors as well as regulators of early viral transcription. The functions of the E5 and E1^E4 proteins are still largely unknown, but these proteins have been implicated in modulating late viral functions. The L1 and L2 proteins form icosahedral capsids for progeny virion generation. The characterization of the cellular targets of these viral proteins and the mechanisms regulating the differentiation-dependent viral life cycle remain active areas for the study of these important human pathogens.

* Corresponding author. Mailing address: Department of Microbiology-Immunology, The Fineberg Medical School, Northwestern University, 303 E. Chicago Ave., Chicago IL 60611. Phone: (312) 503-0648. Fax: (312) 503-0649. E-mail: l-laimins{at}northwestern.edu.

Microbiology and Molecular Biology Reviews, June 2004, p. 362-372, Vol. 68, No. 2
1092-2172/04/$08.00+0     DOI: 10.1128/MMBR.68.2.362-372.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Appl. Environ. Microbiol. Infect. Immun. Eukaryot. Cell
Mol. Cell. Biol. J. Virol. J. Bacteriol.
ALL ASM JOURNALS

Copyright © 2004 by the American Society for Microbiology. All rights reserved.