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Researchers have discovered the first African hantavirus, a type of rodent-borne virus that can cause life-threatening infections in humans when it is inhaled through aerosolized rodent urine or droppings.

A team led by Jan ter Meulen while he was a Howard Hughes Medical Institute (HHMI) international research scholar at the University of Conakry in the Republic of Guinea, identified the new virus in an African wood mouse (Hylomiscus simus) in Sangassou, Guinea. Their findings are published in the May 2006 issue of the journal Emerging Infectious Diseases, published early online on April 18, 2006.

"This discovery represents the first genetic evidence for the presence of hantaviruses in Africa," said ter Meulen, who also holds a position at the University of Leiden in the Netherlands. "This novel hantavirus is related to viruses that cause severe disease in humans in Central and Eastern Europe."

European and Asian hantaviruses cause hemorrhagic fever with renal syndrome (HFRS), a group of similar illnesses with symptoms including, fever, kidney failure, and bleeding. The viruses are carried by a number of rodents, including the brown rat, the striped field mouse, and the yellow-necked mouse. If left untreated, mortality can be as high as 15 percent.

Hantavirus was not seen in the Americas until 1993, when it killed approximately 20 people in the western United States. The American virus causes hantavirus pulmonary syndrome: fever, chills, and severe muscle pain, followed by respiratory distress. Nearly four in 10 cases are fatal. Initially called "Four Corners Disease," the malady was later traced to a previously unknown hantavirus carried by the deer mouse.

The team has suggested calling the virus they found the Sangassou virus, for the region in which it was found. This follows tradition; in 1976, the first hantavirus was found near--and named for--the Hantaan River near Seoul, South Korea.

"We don't yet know what symptoms the Sangassou virus might cause or how virulent it is," said ter Meulen, "but we have already obtained preliminary evidence that the Sangassou virus can infect humans, because we identified hantavirus-specific neutralizing antibodies in [the blood] of humans living in the area where the virus was detected. We do not know if these people suffered from an HFRS-like illness, but studies to determine this are in progress."

Ter Meulen said, however, that there's little cause for alarm; this is not the next bird flu. Like each of the more than two dozen other types of hantavirus, Sangassou virus is carried by only one host species--limiting its spread to the natural range of the African wood mouse, from southern Guinea across parts of Sierra Leone, Liberia, and Ivory Coast, to Ghana.

This one-to-one pairing of virus with host also means that the Sangassou discovery has implications for rodent classification, said ter Meulen. "According to the co-evolution hypothesis, the phylogeny (evolutionary history) of viruses that are restricted to a host species mirrors the phylogeny of their respective hosts," he explained. "So the discovery of an African hantavirus will significantly advance the understanding of hantavirus evolution and of rodent evolution."

The researchers originally collected hundreds of African rodents during a study of the variability of Lassa virus--another rodent-borne virus--in its hosts and in humans. They started looking for an African hantavirus in their unique, West African rodent collection because no hantaviruses had previously been reported from Africa, and they had the technology for detecting unknown hantaviruses. "We are also planning to look for other emerging viruses in our rodent collection," said ter Meulen.

To isolate the virus, the team collected blood samples from more than 600 rodents. Using a technique called reverse-transcriptase polymerase chain reaction (RT-PCR), the scientists searched each sample for a segment of RNA characteristic of hantaviruses. They found a match in one of the four African wood mice in the study.

After finding the virus, the group cloned and sequenced it and compared it with known hantaviruses. The new virus shares approximately 75 percent of its nucleotides and 85 percent of its amino acids with Asian and European hantaviruses. "Those observed differences are large enough to allow its classification as a novel hantavirus," said ter Meulen. The new virus appears most closely related to the Dobrava virus, originally discovered in Slovenia.

The researchers have also grown the virus in cell culture, which is notoriously difficult to do with hantaviruses. Now they can easily test to see which antibodies react with the virus and how strongly they react. Antibody reactivity comparisons are another way to determine genetic relationships among viruses. Isolation of the virus is also required for development of a vaccine.

The scientists also are planning to develop and assess a diagnostic test for infection. The work will be done in Guinea, where the group operates an HHMI-supported virological laboratory.

"Other researchers will probably now screen their rodent biopsy collections for similar African hantaviruses based on the sequence information of the Sangassou virus," said ter Meulen.

In addition to ter Meulen, authors of the article detailing the discovery include Boris Klempa, Detlev Kruger, Brita Auste and Helga Meisel, from the Institute of Virology of the Charité in Berlin (Klempa is also affiliated with the Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic); Elisabeth Fichet-Calvet and Christiane Denys of the Museum of Natural History, Paris; Emilie Lecompte of the Institute of Virology, Philipps University, Marburg, Germany; Vladimir Aniskin of the Severtsov Institute of Ecology and Evolution, Moscow; and Lamine Koivogui of the Viral Hemorrhagic Fever Project, Conakry, Guinea.

Source : Howard Hughes Medical Institute

April 19, 2006 10:31 AMMicrobiology




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