Int J Biochem Mol Biol 2012;3(1):70-85

Original Article
The HIV-1 passage from cytoplasm to nucleus: the process involving a complex
exchange between the components of HIV-1 and cellular machinery to access nucleus
and successful integration

Kallesh Danappa Jayappa, Zhujun Ao, Xiaojian Yao

Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB,
Canada

Received January 9, 2012; accepted February 22, 2012; Epub February 25, 2012; Published March 30, 2012

Abstract: The human immunodeficiency virus 1 (HIV-1) synthesizes its genomic DNA in cytoplasm as soon as it enters into cell. The newly
synthesized DNA remains associated with viral/cellular proteins as a high molecular weight pre-integration complex (PIC), which precludes
passive diffusion across intact nuclear membrane. However, HIV-1 successfully overcomes nuclear membrane barrier by actively delivering its
DNA into nucleus with the help of host nuclear import machinery. Such ability allows HIV-1 to productively infect non-dividing cells as well as
dividing cells at interphase. Further, HIV-1 nuclear import is also found important for the proper integration of viral DNA. Thus, nuclear import
plays a crucial role in establishment of infection and disease progression. While several viral components, including matrix, viral protein R,
integrase, capsid, and central DNA flap are implicated in HIV-1 nuclear import, their molecular mechanism remains poorly understood. In this
review, we will elaborate the role of individual viral factors and some of current insights on their molecular mechanism(s) associated with HIV-1
nuclear import. In addition, we will discuss the importance of nuclear import for subsequent step of viral DNA integration. Hereby we aim to
further our understanding on molecular mechanism of HIV-1 nuclear import and its potential usefulness for anti-HIV-1 strategies.
(IJBMB1201005)
.

Keywords: HIV-1, nuclear import, integrase, matrix, viral protein R, capsid, importin


Address all correspondence to:
Dr. Xiaojian Yao
#508 BMSB, University of Manitoba
745 William Avenue
Winnipeg, MB, Canada. R3E 0J9.
Phone: 204-977-5677; Fax: 204-789-3926
E-mail: yao2@cc.umanitoba.ca
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