Characterizing a Novel Protein in Chikungunya Virus (2016)

Undergraduates: Enrique Toloza, Jennifer McGraw, Heather Vincent Kenneth Plante, Clayton Morrison, Michael Khayat, Kristin Long, Nathaniel Moorman, Mark Heise

Faculty Advisor: Mark Heise
Department: Physics & Astronomy

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Alphaviruses, such as chikungunya virus (CHIKV), are emerging pathogens behind numerous epidemics in recent decades, spurring increased public health interest in alphavirus research and vaccine development. Previous analyses of the alphavirus genome have determined that members of the genus encode ten proteins, all of which are expressed from a positive-strand RNA genome. Our efforts to identify additional proteins in the CHIKV genome have uncovered evidence of a possible eleventh protein in the virus's infection cycle, designated "NORF" (Negative-strand Open Reading Frame). This protein has no known homologs and appears to be expressed from the negative-strand RNA, challenging the current schema of alphavirus protein coding capacity. We have confirmed that the proposed NORF reading frame can be ectopically expressed and detected transient expression of a protein corresponding to NORF during the early stages of the viral replication cycle. Viral mutants with a nonsense mutation in NORF exhibit a growth defect that suggests that NORF is involved in mammalian host immune response modulation. The demonstration of a novel protein expressed from the alphavirus negative-strand RNA represents a significant advance in the current understanding of alphavirus biology and indicates that NORF is a potential target for interference in novel anti-viral therapies.