Protectin D1 Prevents Bird Flu Infection in Mouse Model

The omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator glycoprotein protectin D1 (PD1) prevents infection by the influenza virus, including the deadly H5N1 strain of bird flu, in a mouse model.

Around 60% of humans known to have been infected with the current Asian strain of bird flu (H5N1) have died from it, and virologists fear that H5N1 may mutate or undergo an antigenic shift into a strain capable of efficient human-to-human transmission.

PD1, which is also known as CD59 complement regulatory protein, is a cell surface glycoprotein that regulates complement-mediated cell lysis and is involved in lymphocyte signal transduction. This protein is a potent inhibitor of the complement membrane attack complex, whereby it binds complement C8 and/or C9 during the assembly of this complex, thereby inhibiting the incorporation of multiple copies of C9 into the complex, which is necessary for osmolytic pore formation. Viruses such as HIV, human cytomegalovirus, and vaccinia incorporate host cell PD1 into their own viral envelope to prevent lysis by complement. PD1 also plays a role in signal transduction pathways in the activation of T-cells.

Investigators at Akita University (Japan) screened compounds for their ability to inhibit influenza virus replication in human lung tissue. The most active compound they found was PD1. Results published in the March 7, 2013, online edition of the journal Cell revealed that PD1 markedly lessened influenza virus replication via RNA export machinery. Production of PD1 was suppressed during severe influenza, and PD1 levels inversely correlated with the pathogenicity of H5N1 viruses. PD1 treatment improved the survival and pathology of mice with severe influenza infection, even under conditions where known antiviral drugs failed to protect from death.

"Given the potential for future lethal pandemics, effective drugs are needed for the treatment of severe influenza, such as that caused by H5N1 viruses," said senior author Dr. Yumiko Imai, professor of experimental medicine at Akita University. "We have identified a novel therapeutic target for the treatment of severe influenza that is effective under conditions where known antiviral drugs fail to protect from death. Our findings suggest that PD1could serve as a biomarker as well as a much needed antiviral drug for severe and lethal influenza virus infections."

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Akita University