This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yuste, E.
Right arrow Articles by Domingo, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yuste, E.
Right arrow Articles by Domingo, E.

 Previous Article  |  Next Article 

Journal of Virology, October 2000, p. 9546-9552, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Unusual Distribution of Mutations Associated with Serial Bottleneck Passages of Human Immunodeficiency Virus Type 1

Eloisa Yuste,1 Cecilio López-Galíndez,2 and Esteban Domingo1,*

Centro de Biología Molecular "Severo Ochoa," Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid,1 and Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid,2 Spain

Received 8 May 2000/Accepted 18 July 2000

Repeated bottleneck passages result in fitness losses of RNA viruses. In the case of human immunodeficiency virus type 1 (HIV-1), decreases in fitness after a limited number of plaque-to-plaque transfers in MT-4 cells were very drastic. Here we report an analysis of entire genomic nucleotide sequences of four HIV-1 clones derived from the same HIV-1 isolate and their low-fitness progeny following 7 to 15 plaque-to-plaque passages. Clones accumulated 4 to 28 mutations per genome, with dominance of A right-arrow G and G right-arrow A transitions (57% of all mutations) and 49% nonsynonymous replacements. One clone---but not three sibling clones---showed an overabundance of G right-arrow A transitions, evidencing the highly stochastic nature of some types of mutational bias. The distribution of mutations along the genome was very unusual in that mutation frequencies in gag were threefold higher than in env. Particularly striking was the complete absence of replacements in the V3 loop of gp120, confirmed with partial nucleotide sequences of additional HIV-1 clones subjected to repeated bottleneck passages. The analyses revealed several amino acid replacements that have not been previously recorded among natural HIV-1 isolates and illustrate how evolution of an RNA virus genome, with regard to constant and variable regions, can be profoundly modified by alterations in population dynamics.

* Corresponding author. Mailing address: Centro de Biología Molecular "Severo Ochoa," Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. Phone: 34-91-397 8485. Fax: 34-91-397 4799. E-mail: edomingo{at}cbm.uam.es.

Journal of Virology, October 2000, p. 9546-9552, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • da Silva, J. (2009). Amino Acid Covariation in a Functionally Important Human Immunodeficiency Virus Type 1 Protein Region Is Associated With Population Subdivision. Genetics 182: 265-275 [Abstract] [Full Text]  
  • de la Iglesia, F., Elena, S. F. (2007). Fitness Declines in Tobacco Etch Virus upon Serial Bottleneck Transfers. J. Virol. 81: 4941-4947 [Abstract] [Full Text]  
  • da Silva, J. (2006). Site-Specific Amino Acid Frequency, Fitness and the Mutational Landscape Model of Adaptation in Human Immunodeficiency Virus Type 1. Genetics 174: 1689-1694 [Abstract] [Full Text]  
  • Arien, K. K., Abraha, A., Quinones-Mateu, M. E., Kestens, L., Vanham, G., Arts, E. J. (2005). The Replicative Fitness of Primary Human Immunodeficiency Virus Type 1 (HIV-1) Group M, HIV-1 Group O, and HIV-2 Isolates. J. Virol. 79: 8979-8990 [Abstract] [Full Text]  
  • Yuste, E., Borderia, A. V., Domingo, E., Lopez-Galindez, C. (2005). Few Mutations in the 5' Leader Region Mediate Fitness Recovery of Debilitated Human Immunodeficiency Type 1 Viruses. J. Virol. 79: 5421-5427 [Abstract] [Full Text]  
  • Li, H., Roossinck, M. J. (2004). Genetic Bottlenecks Reduce Population Variation in an Experimental RNA Virus Population. J. Virol. 78: 10582-10587 [Abstract] [Full Text]  
  • Lazaro, E., Escarmis, C., Perez-Mercader, J., Manrubia, S. C., Domingo, E. (2003). Resistance of virus to extinction on bottleneck passages: Study of a decaying and fluctuating pattern of fitness loss. Proc. Natl. Acad. Sci. USA 100: 10830-10835 [Abstract] [Full Text]  
  • Liang, X.-Z., Lee, B. T. K., Wong, S.-M. (2002). Covariation in the Capsid Protein of Hibiscus Chlorotic Ringspot Virus Induced by Serial Passaging in a Host That Restricts Movement Leads to Avirulence in Its Systemic Host. J. Virol. 76: 12320-12324 [Abstract] [Full Text]  
  • Lazaro, E., Escarmis, C., Domingo, E., Manrubia, S. C. (2002). Modeling Viral Genome Fitness Evolution Associated with Serial Bottleneck Events: Evidence of Stationary States of Fitness. J. Virol. 76: 8675-8681 [Abstract] [Full Text]  
  • Pariente, N., Sierra, S., Lowenstein, P. R., Domingo, E. (2001). Efficient Virus Extinction by Combinations of a Mutagen and Antiviral Inhibitors. J. Virol. 75: 9723-9730 [Abstract] [Full Text]  
  • Janini, M., Rogers, M., Birx, D. R., McCutchan, F. E. (2001). Human Immunodeficiency Virus Type 1 DNA Sequences Genetically Damaged by Hypermutation Are Often Abundant in Patient Peripheral Blood Mononuclear Cells and May Be Generated during Near-Simultaneous Infection and Activation of CD4+ T Cells. J. Virol. 75: 7973-7986 [Abstract] [Full Text]  
  • Schneider, W. L., Roossinck, M. J. (2001). Genetic Diversity in RNA Virus Quasispecies Is Controlled by Host-Virus Interactions. J. Virol. 75: 6566-6571 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»