HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kubota, R. Articles by Izumo, S. Search for Related Content PubMed PubMed Citation Articles by Kubota, R. Articles by Izumo, S.

Genetic Stability of Human T Lymphotropic Virus Type I despite Antiviral Pressures by CTLs¹

Ryuji Kubota^2,*, Kousuke Hanada, Yoshitaka Furukawa, Kimiyoshi Arimura, Mitsuhiro Osame, Takashi Gojobori and Shuji Izumo^*

^* Center for Chronic Viral Diseases, Division of Blood Transfusion Medicine, and Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; and Center for Information Biology, National Institutes of Genetics, Shizuoka, Japan

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurological disease. Patients with HAM/TSP show high proviral load despite increased HTLV-I Tax-specific CTL. It is still unknown whether the CTL efficiently eliminate the virus in vivo and/or whether a naturally occurring variant virus becomes predominant by escaping from the CTL. To address these issues, we sequenced a large number of HTLV-I tax genes from HLA-A*02 HAM/TSP patients and estimated synonymous and nonsynonymous changes of the genes to detect positive selection pressure on the virus. We found the pressures in three of six CTL epitopes in HTLV-I Tax, where amino acid substitutions preferentially occurred. Although some of variant viruses were not recognized by the CTL, no variant viruses accumulated within 3–8 years, indicating genetic stability of HTLV-I tax gene. These results suggest that CTL eliminate the infected cells in vivo and naturally occurring variant viruses do not predominate. As Tax is a regulatory protein which controls viral replication, the amino acid substitutions in Tax may reduce viral fitness for replication. Viral fitness and host immune response may contribute to the viral evolution within the infected individuals. Furthermore, the genetic stability in the epitopes despite the antiviral pressures suggests that the three epitopes can be the candidate targets for HTLV-I vaccine development.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Grant-in-Aid for Research on Brain Science of the Ministry of Health, Labor and Welfare of Japan, and a Grant-in-Aid for Scientific Research of the Ministry of Education, Culture, Sports, Science and Technology of Japan.

² Address correspondence and reprint requests to Dr. Ryuji Kubota, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. E-mail address: kubotar{at}m2.kufm.kagoshima-u.ac.jp

³ Abbreviations used in this paper: HTLV-I, human T lymphotropic virus type I; HAM/TSP, HTLV-I-associated myelopathy/tropical spastic paraparesis; Cn, count of nonsynonymous substitutions; Cs, count of synonymous substitutions; sN, nonsynonymous site; sS, synonymous site.

This article has been cited by other articles:

				F. Toulza, A. Heaps, Y. Tanaka, G. P. Taylor, and C. R. M. Bangham High frequency of CD4+FoxP3+ cells in HTLV-1 infection: inverse correlation with HTLV-1-specific CTL response Blood, May 15, 2008; 111(10): 5047 - 5053. [Abstract] [Full Text] [PDF]