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Journal of Virology, February 2006, p. 1242-1249, Vol. 80, No. 3
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.3.1242-1249.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Effects of Gag Mutation and Processing on Retroviral Dimeric RNA Maturation

William Fu,¹ Que Dang,^1,2 Kunio Nagashima,³ Eric O. Freed,¹ Vinay K. Pathak,¹ and Wei-Shau Hu^1*

HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, Maryland 21702,¹ Department of Microbiology, Immunology, and Cell Biology, School of Medicine, West Virginia University, Morgantown, West Virginia 26505,² SAIC-Frederick, Frederick, Maryland 21702³

Received 8 September 2005/ Accepted 7 November 2005

After their release from host cells, most retroviral particles undergo a maturation process, which includes viral protein cleavage, core condensation, and increased stability of the viral RNA dimer. Inactivating the viral protease prevents protein cleavage; the resulting virions lack condensed cores and contain fragile RNA dimers. Therefore, protein cleavage is linked to virion morphological change and increased stability of the RNA dimer. However, it is unclear whether protein cleavage is sufficient for mediating virus RNA maturation. We have observed a novel phenotype in a murine leukemia virus capsid mutant, which has normal virion production, viral protein cleavage, and RNA packaging. However, this mutant also has immature virion morphology and contains a fragile RNA dimer, which is reminiscent of protease-deficient mutants. To our knowledge, this mutant provides the first evidence that Gag cleavage alone is not sufficient to promote RNA dimer maturation. To extend our study further, we examined a well-defined human immunodeficiency virus type 1 (HIV-1) Gag mutant that lacks a functional PTAP motif and produces immature virions without major defects in viral protein cleavage. We found that the viral RNA dimer in the PTAP mutant is more fragile and unstable compared with those from wild-type HIV-1. Based on the results of experiments using two different Gag mutants from two distinct retroviruses, we conclude that Gag cleavage is not sufficient for promoting RNA dimer maturation, and we propose that there is a link between the maturation of virion morphology and the viral RNA dimer.

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* 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.

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Journal of Virology, February 2006, p. 1242-1249, Vol. 80, No. 3
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.3.1242-1249.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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