Newly Discovered Interferon Response May Offer Early Control of H5N1 Influenza Virus
Researchers from Georgia suggest that the cell-signaling protein, interferon type 1, reduced H5N1 influenza virus replication in mice and may offer some degree of protection in the early stages of infection. They report their findings in the June 2009 issue of the Journal of Virology.
Highly pathogenic avian influenza H5N1 viruses increasingly pose a serious public health risk as cases of interspecies transmission from birds to humans continue to rise. Over 400 laboratory-confirmed human cases and 250 deaths from H5N1 virus infection have been reported since 2003. Much is still unknown about the pathogenic mechanisms of H5N1 influenza viruses, but prior research suggests that their ability to evade innate immune responses within the host, such as the type 1 interferon (IFN-a/B) response, contributes to the virulence of these viruses in mammals.
In the study researchers used a mouse model to analyze the role of type 1 interferons in IFN a/β receptor-deficient and wild-type mice challenged with two avian influenza A viruses isolated from humans (HK/483 and HK/486). These two viruses generally exhibit high and low lethality in mice. Results showed that INF-a/β receptor-deficient mice lost significantly more weight and were faster to succumb to death than wild-type mice. Both the HK/483 and H/K 486 virus caused a similar systemic infection in INF-a/β receptor-deficient mice, however, pretreatment with IFN-a/β significantly reduced replication of both viruses.
"These results suggest a role for the IFN-a/β response in the control of H5N1 virus replication both in vivo and in vitro, and as such it may provide some degree of protection to the host in the early stages of infection," say the researchers.
(K.J. Szretter, S. Gangappa, J.A. Belser, H. Zeng, H. Chen, Y. Matsuoka, S. Sambhara, D.E. Swayne, T.M. Tumpey, J.M. Katz. 2009. Early control of H5N1 influenza virus replication by the type 1 interferon response in mice. Journal of Virology, 83. 11: 5825-5834.)
Newly Developed Antimicrobial Peptide May Protect Mice from Lethal Bacterial Infections Including MRSA
In a new study researchers from Japan suggest that a synthetic antimicrobial peptide identified as L5 may prevent death in mice suffering from life-threatening bacterial infections, such as MRSA, by activating the host immune response. They report their findings in the June 2009 issue of the journal Antimicrobial Agents and Chemotherapy.
Innate immunity, the universal defense system shared by all animals, activates when the body responds to foreign pathogens at an early stage of infection. Cationic antimicrobial peptides (known for their antibacterial, antifungal, antiviral, antiprotozoal and antiseptic properties) are part of the innate immune response which kills microorganisms.
In a previous study researchers developed the cationic antimicrobial peptide L5 out of antibacterial proteins from Sarcophaga peregrina and found it to be an effective prophylactic treatment of MRSA in infected mice. In this study mice were administered intra-abdominal implantation as well as normal injections of L5 and observed for its ability to prevent death when challenged with lethal bacterial infections. Results showed that treatments with L5 were highly effective in preventing death when inoculated with Staphylococcus aureus Smith, Enterococcus faecalis SR1004, and Escherichia coli EC14. More specifically, normal injections of L5 prior to infection greatly reduced rates of death and intra-abdominal administration of L5 increased antibacterial activity in the abdominal cavity.
"In conclusion, we found that L5 induced the activation of the host immune responses and protected the mice from death due to infection," say the researchers. "We propose a novel therapeutic intervention that activates the host immunity in infectious diseases and has an advantage in treatment of antibiotic-resistant bacterial infection."
(Y. Okuyama-Nishida, N. Akiyama, G. Sugimori, K. Nomura, K. Ogawa, K.J. Homma, K. Sekimizu, M. Tsujimoto, S. Natori. 2009. Prevention of death in bacterium-infected mice by a synthetic antimicrobial peptide, L5, through activation of host immunity. Antimicrobial Agents and Chemotherapy, 53. 6: 2510-2516.)
New Vaccination Strategy May Protect Against Both Lethal 1918 and H5N1 Influenza Viruses
A new study suggests that vaccination with 1918 H1N1 influenza virus-like particles not only protected mice and ferrets against the lethal 1918 influenza virus, but also displayed cross-reactive immunity against the potentially pandemic H5N1 influenza virus. The researchers from the National Center for Immunization and Respiratory Diseases, Collaborating Centers for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and Novavax, Inc., Rockville, Maryland report their findings in the June 2009 issue of the Journal of Virology.
More than 220,000 hospitalizations and approximately 36,000 deaths are attributed to influenza A viruses each year. Since the first confirmed human cases of avian influenza in 1997, more than 400 additional human H5N1 infections have occurred of which an estimated 60% have been fatal. As new subtypes continue to emerge and the threat of a pandemic is at its highest in decades, researchers are pursuing vaccine strategies that can induce cross-reactive immunity against multiple strains of influenza viruses.
In prior research virus-like particle (VLP) vaccines have proven to be a promising new technology at preventing diseases in humans. VLPs resemble their live-virus counterparts and are readily processed by the immune system, however, they lack the RNA required for virus replication.
In this study researchers generated VLPs from the structural proteins of the 1918 H1N1 virus and compared their ability to protect mice and ferrets against a reconstructed 1918 virus and the highly pathogenic avian H5N1 virus that was isolated from a fatal human case. When immunized twice intranasally with H1N1 VLPs mice were highly protected against a lethal challenge with both the 1918 and H5N1 virus. In contrast, mice receiving two intramuscular immunizations of 1918 VLPs were only protected against the 1918 viral challenge. Mucosal vaccination with 1918 VLPs induced higher levels of cross-reactivity in mice and complete survival in ferrets challenged with a lethal dose of the H5N1 virus. Only a 50% survival rate was noted in intramuscularly immunized animals.
"These results suggest a strategy of VLP vaccination against a pandemic virus and one that stimulates heterotypic immunity against an influenza virus strain with threatening pandemic potential," say the researchers.
(L.A. Perrone, A. Ahmad, V. Veguilla, X. Lu, G. Smith, J. M. Katz, P. Pushko, T.M. Tumpey. 2009. Intranasal vaccination with 1918 influenza virus-like particles protects mice and ferrets from lethal 1918 and H5N1 influenza virus challenge. Journal of Virology, 83. 11: 5726-5734.)
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