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Journal of Virology, June 2000, p. 5729-5735, Vol. 74, No. 12
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Impact of Human Immunodeficiency Virus Type 1 RNA Dimerization on Viral Infectivity and of Stem-Loop B on RNA Dimerization and Reverse Transcription and Dissociation of Dimerization from Packaging

Ni Shen,1,2 Louis Jetté,1 Chen Liang,1 Mark A. Wainberg,1,3 and Michael Laughrea1,2,*

McGill AIDS Centre, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital,1 and Department of Medicine2 and Department of Microbiology and Immunology,3 McGill University, Montreal, Quebec, Canada H3T 1E2

Received 23 September 1999/Accepted 17 March 2000

The kissing-loop domain (KLD) encompasses a stem-loop, named kissing-loop or dimerization initiation site (DIS) hairpin (nucleotides [nt] 248 to 270 in the human immunodeficiency virus type 1 strains HIV-1Lai and HIV-1Hxb2), seated on top of a 12-nt stem-internal loop called stem-loop B (nt 243 to 247 and 271 to 277). Destroying stem-loop B reduced genome dimerization by ~50% and proviral DNA synthesis by ~85% and left unchanged the dissociation temperature of dimeric genomic RNA. The most affected step of reverse transcription was plus-strand DNA transfer, which was reduced by ~80%. Deleting nt 241 to 256 or 200 to 256 did not reduce genome dimerization significantly more than the destruction of stem-loop B or the DIS hairpin. We conclude that the KLD is nonmodular: mutations in stem-loop B and in the DIS hairpin have similar effects on genome dimerization, reverse transcription, and encapsidation and are also "nonadditive"; i.e., a larger deletion spanning both of these structures has the same effects on genome dimerization and encapsidation as if stem-loop B strongly impacted DIS hairpin function and vice versa. A C258G transversion in the palindrome of the kissing-loop reduced genome dimerization by ~50% and viral infectivity by ~1.4 log. Two mutations, CGCG261right-arrowUUAA261 (creating a weaker palindrome) and a Delta 241-256 suppressor mutation, were each able to reduce genome dimerization but leave genome packaging unaffected.

* Corresponding author. Mailing address: Lady Davis Institute for Medical Research, 3755 Cote Ste. Catherine Rd., Montreal, Quebec, Canada H3T 1E2. Phone: (514) 340-8260. Fax: (514) 340-7502. E-mail: laughrea{at}hotmail.com.

Journal of Virology, June 2000, p. 5729-5735, Vol. 74, No. 12
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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