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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.
- Source :
-
Journal of virology [J Virol] 2009 Jan; Vol. 83 (2), pp. 1105-14. Date of Electronic Publication: 2008 Nov 12. - Publication Year :
- 2009
-
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 Gag proteins. 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 human immunodeficiency virus type 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.
- Subjects :
- Amino Acid Substitution genetics
Cell Line, Tumor
Endogenous Retroviruses genetics
Gene Order
Gene Products, gag genetics
Genetic Complementation Test
Humans
Proviruses genetics
Sequence Analysis, DNA
Endogenous Retroviruses physiology
Gene Products, gag physiology
Mutation, Missense
Proviruses physiology
Virus Replication
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 83
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 19004950
- Full Text :
- https://doi.org/10.1128/JVI.01439-08