New Findings!

Marburg in Angola

On March 21, 2005, the Centers for Disease Control (CDC) in Atlanta identified Marburg virus in blood samples sent from patients in Angola. The outbreak was centered around the Uige Province and the samples were sent after patients began dying rapidly from a hemorrhagic fever caused by an unknown disease. This marked the first time that Marburg had been seen in Angola. By May there had been over 270 cases with a fatality rate reaching 92%. Officials from the World Health Organization (WHO) left immediately to help control the outbreak, but one of their biggest barriers was fear. The local population was scared of the disease, scared of the hospital, and now scared of the newly arrived people with their gear. The officials had build trust in the community before they could obtain local cooperation. In order to contain the outbreak, they needed to establish rapid detection of cases and isolation of patients, tracing and care of contacts, infection control in hospitals, and avoidance of funeral and burial practices that allow close contact with bodies. It took until November before this could be done and the outbreak was officially over, but it was not before much death and suffering occurred.

Ndayimirije et al. “Marburg Hemorrhagic Fever in Angola — Fighting Fear and a Lethal Pathogen.” New England Journal of Medicine. Volume 352:2155-2157. Number 21. May 26, 2005.

Potential for Filovirus Vaccine

Researchers have long been searching for a way to prevent filovirus infection as it has a high mortality rate and there is little available in terms of treatment. It looks as if they might have finally found the answer. Research has shown that the use of virus-like particles (non-infectious, but highly immunogenic) can elicit a strong enough immune response in guinea pigs to protect them against infection with a wild type virus. The vaccine is effective in preventing both genera of filovirus: Ebola and Marburg because the virus-like particles include glycoproteins and the matrix protein VP40 from both viruses. The next phase of research on this potential vaccine is to test its effectiveness in protecting non-human primates against these deadly viruses.

Swenson et al. “Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections.” Vaccine. Volume 23. Issue 23. April 27, 2005. Pages 3033-3042.

Comparison of Ebola virus Zaire and Ebola virus Reston

To date, Ebola virus Reston has not been associated with any known human disease, which considering the morbidity and mortality associated with the three other strains, is rather surprising. In order to better understand this difference, scientists have done an extensive comparison between the genomes of Ebola virus Reston and Ebola virus Zaire, with a focus on replication and transcription strategies. The researchers discovered that the replication strategies of Ebola Reston are strikingly similar to those of Ebola Zaire, using the same proteins despite the distinct differences in pathology that result. Both are able to replicate with only three of the four nucleocapsidproteins, NP, VP 35, and L, but the fourth, VP 30 is required by both for transcription. Scientists were surprised by the high degree of homology between the replication and transcription complexes of the two strains, however Ebola Reston is less efficient in these processes than Ebola Zaire. From here scientists are going to examine whether the delayed replication cycle and reduced virulence are a result of decelerated replication and transcription processes.

Boehmann et al. “A reconstituted replication and transcription system for Ebola virus Reston and comparison with Ebola virus Zaire.” Virology. Volume 332. Issue 1. February 5, 2005. Pages 406-417.

Function of Marburg VP 35

Researchers studying Marburg virus in none other than Marburg, Germany, found that its nucleocapsid protein, VP 35 acts as a cofactor to the viral polymerase and therefore plays a critical role in the transcription and replication for the virus. VP 35 forms a trimeric complex with RNA dependent RNA polymerase (L protein) and the nucleoprotein (NP). It was discovered that viruses mutant for VP 35 were unable to recruit the polymerase to transcribe or replicate the viral RNA. The researchers believe that inhibiting VP 35 might be a potential target for future antiviral drugs for the treatment of Marburg virus infection.

Moller et al. “Homo-oligomerization of Marburgvirus VP35 is essential for its function in replication and transcription.” Journal of Virology. December 2005, p. 14876-14886, Vol. 79, No. 23.

Macrophage and Dendritic Cells effects on Ebola virus Pathogenesis

Recent studies of the pathogenesis of Ebola virus in non-human primates indicates that the many of the severe features of the illness are actually a result of host responses, specifically those of the macrophages and dendritic cells, rather than caused by the virus itself. Once infected, macrophages release proinflammatory cytokines and chemokines that attract additional target cells and increase vasodilation, but are unable to stop virus replication. The infected dendritic cells also release proinflammatory chemokines, but are unable to initiate the antigen specific response they are supposed to. Because of this, the characteristic symptoms of hemorrhagic fever results, while the virus is still able to proliferate and spread throughout the body. However, this provides insight into new methods to control the spread of the virus and the severity of the symptoms. Researchers believe that modifying the host’s immune response to Ebola infection might be a potential therapeutic technique to increase survival.

Bray et al. “Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever.” The International Journal of Biochemistry & Cell Biology Volume 37, Issue 8 , August 2005, Pages 1560-1566.