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Journal of Virology, January 2006, p. 451-459, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.451-459.2006

Mutations in the U5 Sequences Adjacent to the Primer Binding Site Do Not Affect tRNA Cleavage by Rous Sarcoma Virus RNase H but Do Cause Aberrant Integrations In Vivo

Jangsuk Oh, Kevin W. Chang, and Stephen H. Hughes*

HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, Maryland 21702-1201

Received 9 May 2005/ Accepted 9 October 2005

In most retroviruses, the first nucleotide added to the tRNA primer becomes the right end of the U5 region in the right long terminal repeat (LTR); the removal of this tRNA primer by RNase H defines the right end of the linear double-stranded DNA. Most retroviruses have two nucleotides between the 5' end of the primer binding site (PBS) and the CA dinucleotide that will become the end of the integrated provirus. However, human immunodeficiency virus type 1 (HIV-1) has only one nucleotide at this position, and HIV-2 has three nucleotides. We changed the two nucleotides (TT) between the PBS and the CA dinucleotide of the Rous sarcoma virus (RSV)-derived vector RSVP(A)Z to match the HIV-1 sequence (G) and the HIV-2 sequence (GGT), and we changed the CA dinucleotide to TC. In all three mutants, RNase H removes the entire tRNA primer. Sequence analysis of RSVP(HIV2) proviruses suggests that RSV integrase can remove three nucleotides from the U5 LTR terminus of the linear viral DNA during integration, although this mutation significantly reduced virus titer, suggesting that removing three nucleotides is inefficient. However, the results obtained with RSVP(HIV1) and RSVP(CATC) show that RSV integrase can process and integrate the normal U3 LTR terminus of a linear DNA independently of an aberrant U5 LTR terminus. The aberrant end can then be joined to the host DNA by unusual processes that do not involve the conserved CA dinucleotide. These unusual events generate either large duplications or, less frequently, deletions in the host genomic DNA instead of the normal 5- to 6-base duplications.

* Corresponding author. Mailing address: HIV Drug Resistance Program, NCI at Frederick, P.O. Box B, Bldg. 539, Rm. 130A, Frederick, MD 21702-1201. Phone: (301) 846-1619. Fax: (301) 846-6966. E-mail: Hughes{at}ncifcrf.gov.

Journal of Virology, January 2006, p. 451-459, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.451-459.2006




This article has been cited by other articles:

  • Oh, J., Chang, K. W., Hughes, S. H. (2008). Integration of Rous Sarcoma Virus DNA: a CA Dinucleotide Is Not Required for Integration of the U3 End of Viral DNA. J. Virol. 82: 11480-11483 [Abstract] [Full Text]  
  • Chang, K. W., Oh, J., Alvord, W. G., Hughes, S. H. (2008). The Effects of Alternate Polypurine Tracts (PPTs) and Mutations of Sequences Adjacent to the PPT on Viral Replication and Cleavage Specificity of the Rous Sarcoma Virus Reverse Transcriptase. J. Virol. 82: 8592-8604 [Abstract] [Full Text]  
  • Oh, J., McWilliams, M. J., Julias, J. G., Hughes, S. H. (2008). Mutations in the U5 Region Adjacent to the Primer Binding Site Affect tRNA Cleavage by Human Immunodeficiency Virus Type 1 Reverse Transcriptase In Vivo. J. Virol. 82: 719-727 [Abstract] [Full Text]  
  • Oh, J., Chang, K. W., Wierzchoslawski, R., Alvord, W. G., Hughes, S. H. (2008). Rous Sarcoma Virus (RSV) Integration In Vivo: a CA Dinucleotide Is Not Required in U3, and RSV Linear DNA Does Not Autointegrate. J. Virol. 82: 503-512 [Abstract] [Full Text]  
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  • Oh, J., Chang, K. W., Alvord, W. G., Hughes, S. H. (2006). Alternate polypurine tracts affect rous sarcoma virus integration in vivo.. J. Virol. 80: 10281-10284 [Abstract] [Full Text]  


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