Regulation of Viral Intermediate Gene Expression by the Vaccinia Virus B1 Protein Kinase

Abstract

The B1 gene of vaccinia virus encodes a serine/threonine protein kinase that is expressed early after infection. Under nonpermissive conditions, temperature-sensitive mutants (ts2 and ts25) that map to B1 fail to efficiently replicate viral DNA. Studies on the regulation of intracellular processes involved in eukaryotic nucleic acid metabolism have pointed to protein phosphorylation as playing a key role. Poxviruses have acquired analogs of a number of host cell genes to maintain their autonomy from the cell, including two serine/threonine protein kinases (B1 and F10) and a dual-specificity protein phosphatase (H1). The F10 kinase (22) and H1 phosphatase (15) are expressed late in infection, are incorporated into virions, and play major roles in virion morphogenesis (11,24,38). Interestingly, the H1 phosphatase has been implicated in early gene transcription (24). Mutant virus particles devoid of H1 phosphatase were unable to transcribe early genes either in vivo or in vitro. This finding led us to investigate the role that phosphorylation might play in the transcription of the other gene classes. The B1 kinase is expressed exclusively early in infection; it localizes to viral replication factories and appears to be a minor component of the virion (3,23,34

Vaccinia Virus Nonstructural Protein Encoded by the A11R Gene Is Required for Formation of the Virion Membrane

“…A possible candidate would be the VAC B1 kinase. Although some VAC B1 temperature-sensitive mutants have defects in DNA replication (25) and intermediate gene expression (18) at the nonpermissive temperature, at least one has been described as synthesizing normal amounts of DNA but having aberrant morphogenesis, although the arrest is at the stage of IVs (9,19).…”

VRK1 phosphorylates CREB and mediates CCND1 expression

“…Vaccinia virus B1 (vvB1) kinase plays a critical role in viral DNA replication (Rempel et al, 1990) by regulating intermediate viral gene expression (Kovacs et al, 2001). Human vaccinia-related kinase 1 (VRK1) can functionally rescue the DNA replication deficiency of vaccinia virus harboring a temperature-sensitive mutation of vvB1 under nonpermissive temperature conditions (Boyle and Traktman, 2004).…”

Viral Serine/Threonine Protein Kinases

“…VRK orthologs are present in mam- Nearly all known poxviruses encode B1 orthologs; the exception is molluscum contagiosum virus (199). Although not proven as of yet, it is possible that the molluscum contagiosum virus is able to compensate for the lack of B1 by usurping related host kinases, such as VRKs (108). In line with this idea, expression of the VRK1 genes of humans and, to a lesser extent, mice in the B1-defective ts2 mutant of vaccinia virus rescues the inhibition of DNA replication, virus production, and plaque formation observed with this mutant (24).…”

“…The phenotypes associated with temperature-sensitive mutants of B1 show that the kinase is critically involved in at least two key stages of the virus cycle: DNA replication and production of intermediate viral proteins (108,189).…”