JC virus, as well as the simian polyomavirus SV40.[2]
Sequence and structure
Agnoprotein is typically quite short: examples from
post-translational modifications have been detected.[2][3]
Expression
JC virus, indicating the position of the agnogene (yellow) in the late region relative to the other coding genes and to the non-coding control region (NCCR).[5]
Agnoprotein is expressed from a region of the circular viral
viral capsid proteins and is known as the "late region" because it is expressed late in the cycle of viral infection and replication.[2] The agnogene and its protein product received their name (from the Greek agnosis, "without knowledge"[3]) because the presence of the open reading frame and corresponding RNA was detected before the existence of the protein product was confirmed.[6]
Cellular localization
Agnoprotein is consistently detected in the
perinuclear space. It is also detectable in the cell nucleus; in the case of JC virus, nuclear-localized agnoprotein comprises 15–20% of the total agnoprotein expressed.[2]
Function
Agnoprotein is a
secreted from infected cells, even before viral exit, and taken up by neighboring uninfected cells.[9]
Agnoprotein has been associated with a number of processes in the viral life cycle, including
membrane permeability to facilitate the virus particles' exit from the cell.[10] In addition, effects on the behavior of the host cell itself have been observed, including impaired progression through the cell cycle and deficiencies in DNA repair.[2]
Although agnoprotein is critical for proliferation in the polyomaviruses in which it occurs, its distribution among polyomaviruses whose
sequence conservation.[2][3] Additional predicted agnogenes have been identified from the sequenced genomes of other polyomaviruses, and the predicted protein products vary considerably in length and have low sequence identity overall.[3]
The distribution of agnoprotein among polyomaviruses has prompted speculation that there is little
selection pressure in favor of its presence. Among sequenced BK virus genomes, agnoprotein is the most variable viral protein in amino acid sequence.[3] Differences in tissue tropism and in viral life cycle, particularly in viral exit from the host cell, have also been proposed as explanations for the presence or absence of agnoprotein in various human polyomaviruses.[14]
Avian polyomaviruses
A gene occurs in avian polyomaviruses in a similar genomic position and was originally annotated as an agnogene, but it has no detectable sequence similarity to the mammalian examples. The protein product of this gene has been detected in the capsids of mature virions, leading to its reclassification as VP4 to reflect its distinct role as a
structural protein. However, it is still often referred to as "avian agnoprotein 1a".[3][15]
