Interesting. I wonder if vaccinia is inhibiting antigen presentation via its apoptotic mimicry strategy of infection.

Vaccinia has been shown to rely on exposed PS to infect cells, in a paper titled Vaccinia Virus Uses Macropinocytosis and Apoptotic Mimicry to Enter Host Cells, (Helenius & Mercer, Science, April 2008).

“The induction of blebs, the endocytic event, and infection were all critically dependent on the presence of exposed phosphatidylserine in the viral membrane.”

Heinrichs, writing in Nature Reviews Molecular Cell Biology wrote, “The [vaccinia] mature virus membrane is known to be enriched in PS, which is required for infection.”

Heinrichs then commented, “By posing as apoptotic bodies, mature [vaccinia]viruses may also avoid immune detection.”

The role of phospholipids in vaccinia entry published in Science was recently confirmed and expanded upon by none other than Bernard Moss, head of the lab of viral diseases at NIAID, in a paper titled, Appraising the apoptotic mimicry model and the role of phospholipids for poxvirus entry, (PNAS, Sept 2009).

These observations should be considered with what is now a large body of evidence demonstrating that exposed PS, an early hallmark of apoptosis, is now understood to be a fundamental inhibitor of an inflammatory response, and an inducer of anti-inflammatory cytokines.

As the apoptotic process was likely necessary to evolve to allow for the possibility of metazoans, could viruses be exploiting what may be our most ancient and basic sign of “self”?

A thorough and open access review on the topic oof PS being immunosuppressive, exploited by many pathogens, and is a promising therapeutic target, was just published last month by a group in Germany who have been targeting PS as potential therapy against enveloped viruses, titled: Phospholipids: Key Players in Apoptosis and Immune Regulation, (Gaipl et al, Molecules).

Meanwhile, other scientists are finding that targeting PS with monoclonal antibodies has broad therapeutic potential against vaccinia and other enveloped viruses, and infected cells (which also expose PS), (Soares et al, Nature Medicine, December 2008), titled: Targeting Inside-Out Phosphatidylserine as a Therapeutic Strategy For Viral Diseases.

The Nature Medicine paper concludes:

“Phosphatidylserine on virions and virally infected cells may enable viruses to evade immune recognition and dampen inflammatory responses to infection.”

“In conclusion, targeting PS on cells infected with multiple different viruses and on virions themselves shows promise as an anti-viral strategy. Because anionic phospholipids on virus-infected cells are host-derived and independent of the viral genome, the acquisition of drug resistance should be less problematic than with agents that target virus-encoded components.”

- now wouldn’t that be nice…

MT