The host phosphoinositide 5-phosphatase SHIP2 regulates dissemination of vaccinia virus

Shannon McNulty1, Kimberly Powell, Christophe Erneux

  • 1Microbiology and Molecular Genetics Graduate Program, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Insights

Poxvirus actin tail formation is regulated by SHIP2, a phosphatase. This protein and viral A34 control virus release, acting as gatekeepers for poxvirus dissemination.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Enveloped poxviruses utilize actin tails for cell-to-cell spread.
  • Host and viral proteins mediate actin tail formation, but release regulation is less understood.

Purpose of the Study:

  • Investigate the role of phosphoinositide 5-phosphatase SHIP2 in poxvirus actin tail formation and release.
  • Determine the relationship between SHIP2, viral protein A34, and virus dissemination.

Main Methods:

  • Localization studies of SHIP2 in infected cells.
  • Analysis of actin tails and virus release in SHIP2-deficient cells.
  • Examination of virus release and SHIP2 recruitment in cells infected with A34 mutant strains.

Main Results:

  • SHIP2 localizes to actin tails, dependent on tyrosine kinases and N-WASP.
  • Cells lacking SHIP2 exhibit normal actin tails but increased virus release.
  • Viral A34 mutations reduce SHIP2 recruitment and enhance virus release, indicating A34's inhibitory role is mediated by SHIP2.

Conclusions:

  • SHIP2 acts as a negative regulator of poxvirus release.
  • SHIP2 and viral A34 function as gatekeepers to control poxvirus spread based on environmental cues.

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Intracellular Movement of Viruses and Bacteria01:10

Intracellular Movement of Viruses and Bacteria

Intracellular bacteria and viruses often comprise a group of highly infectious pathogens that can cause several diseases. Bacterial pathogens include those belonging to the genus Rickettsia responsible for conditions such as rocky mountain spotted fever and the Mediterranean spotted fever; Chlamydia, a genus responsible for a sexually transmitted disease; Coxiella burnetii, an agent responsible for Q fever. Viral pathogens include vaccinia—a poxvirus, and herpes simplex virus—a virus that...
Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...