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Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):E4342-9. doi: 10.1073/pnas.1416122111. Epub 2014 Sep 30.

Human DNA tumor viruses generate alternative reading frame proteins through repeat sequence recoding.

Author information

1
Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213;
2
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033; and.
3
School of Biochemistry, University College Cork, Cork, Ireland.
4
Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213; yc70@pitt.edu psm9@pitt.edu.

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are human DNA tumor viruses that express nuclear antigens [latency-associated nuclear antigen 1 (LANA1) and Epstein-Barr nuclear antigen 1 (EBNA1)] necessary to maintain and replicate the viral genome. We report here that both LANA1 and EBNA1 undergo highly efficient +1/-2 programmed ribosomal frameshifting to generate previously undescribed alternative reading frame (ARF) proteins in their repeat regions. EBNA1(ARF) encodes a KSHV LANA-like glutamine- and glutamic acid-rich protein, whereas KSHV LANA1(ARF) encodes a serine/arginine-like protein. Repeat sequence recoding has not been described previously for human DNA viruses. Programmed frameshifting (recoding) to generate multiple proteins from one RNA sequence can increase the coding capacity of a virus, without incurring a selective penalty against increased capsid size. The presence of similar repeat sequences in cellular genes, such as huntingtin, suggests that a comparison of repeat recoding in virus and human systems may provide functional and mechanistic insights for both systems.

KEYWORDS:

EBV; HHV4; HHV8; POLY-Q; PRF

PMID:
25271323
PMCID:
PMC4205619
DOI:
10.1073/pnas.1416122111
[Indexed for MEDLINE]
Free PMC Article

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