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Advances in Virology
Volume 2012 (2012), Article ID 640894, 14 pages
Review Article

Retrovirus Entry by Endocytosis and Cathepsin Proteases

1Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan
2Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan
3Pathogen Genomic Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan
4Department of Microbiology, National University of Singapore, Singapore 117597

Received 9 August 2012; Revised 14 October 2012; Accepted 6 November 2012

Academic Editor: Jason Mercer

Copyright © 2012 Yoshinao Kubo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Retroviruses include infectious agents inducing severe diseases in humans and animals. In addition, retroviruses are widely used as tools to transfer genes of interest to target cells. Understanding the entry mechanism of retroviruses contributes to developments of novel therapeutic approaches against retrovirus-induced diseases and efficient exploitation of retroviral vectors. Entry of enveloped viruses into host cell cytoplasm is achieved by fusion between the viral envelope and host cell membranes at either the cell surface or intracellular vesicles. Many animal retroviruses enter host cells through endosomes and require endosome acidification. Ecotropic murine leukemia virus entry requires cathepsin proteases activated by the endosome acidification. CD4-dependent human immunodeficiency virus (HIV) infection is thought to occur via endosomes, but endosome acidification is not necessary for the entry whereas entry of CD4-independent HIVs, which are thought to be prototypes of CD4-dependent viruses, is low pH dependent. There are several controversial results on the retroviral entry pathways. Because endocytosis and endosome acidification are complicatedly controlled by cellular mechanisms, the retrovirus entry pathways may be different in different cell lines.