The many faces of the flavivirus non-structural glycoprotein NS1

The flavivirus non-structural protein, NS1 is an enigmatic protein whose structure and mechanistic function has remained elusive since it was first identified in 1970 as a viral antigen circulating in the sera of dengue infected patients. All flavivirus NS1 genes share a high degree of homology, encoding a 352 amino acid polypeptide that has a molecular weight of between 46 and 55 kDa depending on its glycosylation status. NS1 exists in multiple oligomeric forms and is found in different cellular locations; cell membrane associated in vesicular compartments or on the cell surface and as a secreted extracellular hexamer. Intracellular NS1 has been shown to co-localize with dsRNA and other components of the viral replication complex and plays an essential co-factor role in virus replication. However, the precise function of this protein in viral replication has yet to be elucidated. Secreted and cell surface-associated NS1 are highly immunogenic and both the protein and the antibodies it elicits have been implicated in either protection or pathogenesis in infected hosts. It is also an important biomarker for early diagnosis. In this review we provide an overview of these somewhat disparate areas of research