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Journal of Virology, August 2004, p. 8788-8798, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8788-8798.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Endogenous Retrovirus Family HERV-K(HML-5): Status, Evolution, and Reconstruction of an Ancient Betaretrovirus in the Human Genome{dagger}

Laurence Lavie,1 Patrik Medstrand,2 Werner Schempp,3 Eckart Meese,1 and Jens Mayer1*

Department of Human Genetics, University of Saarland, 66421 Homburg,1 Institute of Human Genetics and Anthropology, University of Freiburg, 79106 Freiburg, Germany,3 Department of Cell and Molecular Biology, Lund University, 22184 Lund, Sweden2

Received 27 December 2003/ Accepted 12 April 2004

The human genome harbors numerous distinct families of so-called human endogenous retroviruses (HERV) which are remnants of exogenous retroviruses that entered the germ line millions of years ago. We describe here the hitherto little-characterized betaretrovirus HERV-K(HML-5) family (named HERVK22 in Repbase) in greater detail. Out of 139 proviruses, only a few loci represent full-length proviruses, and many lack gag protease and/or env gene regions. We generated a consensus sequence from multiple alignment of 62 HML-5 loci that displays open reading frames for the four major retroviral proteins. Four HML-5 long terminal repeat (LTR) subfamilies were identified that are associated with monophyletic proviral bodies, implying different evolution of HML-5 LTRs and genes. Sequence analysis indicated that the proviruses formed approximately 55 million years ago. Accordingly, HML-5 proviral sequences were detected in Old World and New World primates but not in prosimians. No recent activity is associated with this HERV family. We also conclude that the HML-5 consensus sequence primer binding site is identical to methionine tRNA. Therefore, the family should be designated HERV-M. Our study provides important insights into the structure and evolution of the oldest betaretrovirus in the primate genome known to date.

* Corresponding author. Mailing address: Department of Human Genetics, Building 60, University of Saarland, Medical Faculty, 66421 Homburg, Germany. Phone: 49 6841 1626627. Fax: 49 6841 1626186. E-mail: jens.mayer{at}uniklinik-saarland.de.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, August 2004, p. 8788-8798, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8788-8798.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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