A single amino acid substitution in a segment of the CA protein within gag that has similarity to human immunodeficiency virus type 1 blocks infectivity of a human endogenous retrovirus K provirus in the human genome

Heslin, D.J., Murcia, P. , Arnaud, F., Van Doorslaer, K., Palmarini, M. and Lenz, J. (2009) A single amino acid substitution in a segment of the CA protein within gag that has similarity to human immunodeficiency virus type 1 blocks infectivity of a human endogenous retrovirus K provirus in the human genome. Journal of Virology, 83(2), (doi: 10.1128/JVI.01439-08)

Abstract

Human Endogenous Retrovirus K (HERV-K) is the most intact retrovirus in the human genome. However no single HERV-K provirus in the human genome today appears to be infectious. Since the Gag protein is the central component for the production of retrovirus particles, we investigated the abilities of Gag from two HERV-K proviruses to support production of virus-like particles and viral infectivity. HERV-K113 has full-length open reading frames for all viral proteins, while HERV-K101 has a full-length gag open reading frame and is expressed in human male germ cell tumors. The Gag of HERV-K101 allowed production of viral particles and infectivity, although at lower levels than observed with a consensus sequence Gag. Thus including HERV-K109, at least two HERV-K proviruses in human genome today have functional Gags. In contrast, HERV-K113 Gag supported only very low levels of particle production and no infectivity was detectable due to a single amino acid substitution (I516M) near the extreme C-terminus of the CA protein within Gag. The sequence of this portion of HERV-K CA showed similarities to that of HIV-1 and other primate immunodeficiency viruses. The extreme C-terminus of CA may be a general determinant of retrovirus particle production. In addition, precise mapping of the defects in HERV-K proviruses as was done here identifies the key polymorphisms that need to be analyzed to assess the possible existence of infectious HERV-K alleles within the human population.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Palmarini, Professor Massimo and Murcia, Professor Pablo
• Authors: Heslin, D.J., Murcia, P., Arnaud, F., Van Doorslaer, K., Palmarini, M., and Lenz, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Journal of Virology
• ISSN: 0022-538X