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Tips from the Journals of the American Society for Microbiology

American Society for Microbiology

Immune Cells May Induce Gastritis During H. pylori Infection

For the first time researchers from Australia and The Netherlands examine the inflammatory response induced by macrophages that may contribute to the development of gastritis during Helicobacter pylori infection in mice. They report their findings in the May 2008 issue of the journal Infection and Immunity.

H. pylori is the causative agent of human chronic gastritis, a condition that often leads to gastrointestinal ulcers and cancer. The gastric mucus found in the human stomach of a H. pylori infection-free adult or child is populated by very few macrophages, however previous research shows that macrophages increase in number in response to H. pylori infection. The mouse model of Helicobacter infection mimics human H. pylori disease in many ways and offers researchers an opportunity to analyze the adaptive immune regulation of Helicobacter-induced chronic gastritis.

Macrophages are defined as white blood cells that are key players in the immune response to foreign invaders. In the study mice were intravenously injected with drug-loaded liposomes to deliberately deplete their spleens and stomachs of macrophages and then infected with H. pylori. Results showed that elimination of macrophages reduced the gastric pathology induced by H. pylori, however it did not affect bacterial presence in the stomach.

"This study demonstrates that macrophages have a central role in Helicobacter infection-induced gastritis but do not affect H. pylori-specific antibody responses," say the researchers. "In identifying a role for macrophages in the initiation of gastritis during H. pylori infection, this study may assist in future studies targeting the inhibition of gastritis in the host and provide a stimulus to study the capacity of macrophage-modifying drugs to reduce the gastritis associated with Helicobacter disease.

(M. Kaparakis, A.K. Walduck, J.D. Price, J.S. Pedersen, N. van Rooijen, M.J. Pearse, O.L.C. Wijburg, R.A. Strugnell. 2008. Macrophages are mediators of gastritis in acute Helicobacter pylori infection in C57BL/6 mice. Infection and Immunity, 76. 5: 2235-2239.)

New Single-Dose Orthopoxvirus Drug in First Stage of Human Trials

Researchers from SIGA Technologies, TransTech Pharma, and INC Research developed a new single-dose antiviral drug against orthopoxvirus that was safely tolerated in humans during phase I trials and could potentially be used to prevent and treat smallpox. They report their findings in the May 2008 issue of the journal Antimicrobial Agents and Chemotherapy.

Prior to eradication, variola virus, the causative agent of smallpox and member of the orthopoxvirus family, was estimated to have killed, crippled, or disfigured up to 10% of the human population. Highly communicable with an exceptionally high morbidity rate, smallpox currently poses a threat as an instrument of biowarfare placing it at the forefront of focus for effective preventative and treatment therapies.

In this phase I study fasting healthy volunteers were administered single oral doses of 500, 1,000, and 2,000 mg of the drug ST-246 and non-fasting healthy volunteers received 1,000 mg. No adverse reactions were observed and no subjects were withdrawn from the study, overall ST-246 was found to be generally well tolerated. Upon further testing, researchers found absorption to be greater in nonfasting volunteers at a rate of approximately 2 to 3 hours and exposure levels to be sufficient for inhibiting orthopoxvirus replication.

"In conclusion, ST-246 is safe and well tolerated when administered orally as a single dose to healthy human volunteers in a fasting state or non-fasting state," say the researchers.

(R. Jordan, D. Tien, T.C. Bolken, K.F. Jones, S.R. Tyavanagimatt, J. Strasser, A. Frimm, M.L. Corrado, P.G. Strome, D.E. Hruby. 2008. Single-dose safety and pharmacokinetics of ST-246, a novel orthopoxvirus egress inhibitor. Antimicrobial Agents and Chemotherapy, 52. 5: 1721-1727.)

New Coronavirus Found in Beluga Whale

Researchers from Washington University School of Medicine, St. Louis, Missouri; Sea Word, San Diego, CA; and the University of California at Davis have determined a never before seen virus found in the liver of a beluga whale to be a new strain of the coronavirus. They report their findings in the May 2008 issue of the Journal of Virology.

With emerging infectious diseases on the rise, it is now estimated that 75% derive from zoonotic sources. This being the case, health officials are now looking to zoological parks and aquariums for emerging virus surveillance.

ViroChip is a panviral DNA testing method capable of detecting thousands of known viruses as well as unknown viruses linked to previously identified viral families. In the study a ViroChip was used to evaluate the liver tissue of a male captive-born beluga whale for viruses following his death after a short illness characterized by pulmonary disease and acute liver failure. Results revealed a highly divergent novel coronavirus deemed most similar to group 3 coronaviruses. The virus has been tentatively named coronavirus SW1.

"We have used a ViroChip to identify a novel coronavirus directly from primary animal tissues," say the researchers. "Furthermore, the identification of a previously unrecognized virus in a captive animal underscores the vast diversity of viruses that remains unexplored in animals."

(K.A. Mihindukulasuriya, G. Wu, J. St. Leger, R.W. Nordhausen, D. Wang. 2008. Identification of a novel coronavirus from a beluga whale by using a panviral microarray. Journal of Virology, 82. 10: 5084-5088.)


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