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Research explained · Herpesvirus proteins

How does the HSV-1 protein ICP0 affect SUMO in a cell’s nucleus?

In the cells studied, an HSV-1 protein called ICP0 drew the host enzyme SENP1 to the same spots in the nucleus. Researchers also saw less SUMO-1 in the nuclei of cells expressing either protein. SUMO-1 can act as a tag on other proteins. The order in which the changes took place remained open. [1]

See original studies View the SGM research record

What the researchers could see and measure

SENP1 by itself
SENP1 was visible in separate spots in the nucleus. Some overlapped with structures marked by a host protein called PML.
The researchers used SENP1’s usual location as a point of comparison when they added ICP0. [1]
ICP0 and SENP1 together
ICP0 recruited SENP1 to nuclear domains when the two were expressed together. A similar pattern was observed early in infection.
The images showed both proteins at the same sites. Direct binding would require different evidence. [1]
Changes in SUMO-1
The researchers saw lower levels of nuclear SUMO-1 with either protein. With SENP1, biochemical tests also showed lower levels of SUMO-1-tagged proteins, including a modified form of PML.
The images located the change in the nucleus. The biochemical tests showed that some of the tagged forms became less abundant. [1]

What are SUMO and ubiquitin?

SUMO and ubiquitin are small proteins that cells can attach to other proteins. SENP1 removes SUMO tags, and ICP0 helps attach ubiquitin to targets. The 2002 study asked whether these processes intersect at the same structures in the nucleus during infection. [1]

Does recruitment establish who acts first?

The authors left open whether cells have to remove SUMO before they add ubiquitin or break down a tagged protein. [1]

Why would the location matter to the virus?

Later experiments found that SUMO interactions helped recruit proteins that suppress HSV-1 infection to sites near incoming viral DNA. Those experiments studied how the cell responds to incoming DNA. SENP1’s role in that response remains a separate question. [1][2]

Original research

  1. Bailey and O’Hare (2002), Journal of General Virology. Herpes simplex virus 1 ICP0 co-localizes with a SUMO-specific protease. Primary localization and SUMO-1 experiments.
  2. Cuchet-Lourenço et al. (2011), PLOS Pathogens. SUMO pathway dependent recruitment of cellular repressors to herpes simplex virus type 1 genomes. Later experiments on recruitment of antiviral host factors.