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

Hyun Jin Kwun, Tuna Toptan, Suzane Ramos Da Silva, John F. Atkins, Patrick S. Moore, Yuan Chang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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. EBNA1ARF encodes a KSHV LANA-like glutamine- and glutamic acid-rich protein, whereas KSHV LANA1ARFencodes 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.

Original languageEnglish (US)
Pages (from-to)E4342-E4349
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
StatePublished - Oct 14 2014

All Science Journal Classification (ASJC) codes

  • General


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