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Journal of Virology, September 2008, p. 8253-8261, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.02663-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Capsid Proteins from Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus SIVmac Can Coassemble into Mature Cores of Infectious Viruses{triangledown}

Jianbo Chen,1 Vinay K. Pathak,1 Weiqun Peng,2 and Wei-Shau Hu1*

HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland 21702,1 Department of Physics, The George Washington University, 725 21st St. NW, Corcoran Hall Room 105, Washington, DC 200522

Received 14 December 2007/ Accepted 16 June 2008

We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5{alpha} protein from the rhesus monkey (rhTRIM5{alpha}) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIVmac CA protein (sCA). If hCA and sCA cannot coassemble into the same core when equal amounts of sCA and hCA are coexpressed, the infectivities of such virus preparations in cells should be inhibited less than twofold by rhTRIM5{alpha}. However, if hCA and sCA can coassemble into the same core structure to form a mixed core, rhTRIM5{alpha} would be able to recognize such cores and significantly restrict virus infectivity. We examined the restriction phenotypes of viruses containing both hCA and sCA. Our results indicate that hCA and sCA can coassemble into the same mature core to produce infectious virus. To our knowledge, this is the first demonstration of functional coassembly of heterologous CA protein into the retroviral core.

* Corresponding author. Mailing address: HIV Drug Resistance Program, NCI-Frederick, P.O. Box B, Building 535, Room 336, Frederick, MD 21702. Phone: (301) 846-1250. Fax: (301) 846-6013. E-mail: whu{at}ncifcrf.gov

{triangledown} Published ahead of print on 25 June 2008.

Journal of Virology, September 2008, p. 8253-8261, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.02663-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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