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Journal of Virology, May 2000, p. 4327-4334, Vol. 74, No. 9
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Dominant Role of Host Selective Pressure in Driving Hepatitis C Virus Evolution in Perinatal Infection

Aldo Manzin,1,* Laura Solforosi,1 Maurizia Debiaggi,2 Francesca Zara,3 Elisabetta Tanzi,4 Luisa Romanò,4 Alessandro R. Zanetti,4 and Massimo Clementi5

Institute of Microbiology, University of Ancona, Ancona,1 Departments of Microbiology2 and Infectious and Tropical Diseases,3 University of Pavia, and I.R.C.C.S. Policlinico S. Matteo, Pavia, Institute of Virology, University of Milan, Milan,4 and Department of Biomedical Sciences, University of Trieste, Trieste,5 Italy

Received 7 September 1999/Accepted 24 January 2000

The dynamics of the genetic diversification of hepatitis C virus (HCV) populations was addressed in perinatal infection. Clonal sequences of hypervariable region 1 of the putative E2 envelope protein of HCV were obtained from four HCV-infected newborns (sequential samples spanning a period of 6 to 13 months after birth) and from their mothers (all samples collected at delivery). The data show that the variants detected between birth and the third month of life in samples from the four newborns were present in the HCV populations of their mothers at delivery. In the newborns, a unique viral variant (or a small group of closely related variants) remained stable for weeks despite active viral replication. Diversification of the intrahost HCV population was observed 6 to 13 months after birth and was substantially higher in two of the four subjects, as documented by the intersample genetic distance (GD) (P = 0.007). Importantly, a significant correlation between increasing GD and high values for the intersample Ka/Ks ratio (the ratio between antonymous and synonymous substitutions; an index of the action of selective forces) was observed, as documented by the increase of both parameters over time (P = 0.01). These data argue for a dominant role of positive selection for amino acid changes in driving the pattern of genetic diversification of HCV populations, indicate that the intrahost evolution of HCV populations is compatible with a Darwinian model system, and may have implications in the designing of future antiviral strategies.

* Corresponding author. Mailing address: Institute of Microbiology, University of Ancona, Via Pietro Ranieri, I-60100 Ancona, Italy. Phone: 39 071 596 4849. Fax: 39 071 596 4852. E-mail: manzin{at}popcsi.unian.it.

Journal of Virology, May 2000, p. 4327-4334, Vol. 74, No. 9
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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