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Ebola Virus / Lassa Fever

Description
Viral hemorrhagic fevers are a group of febrile illnesses caused by several distinct families of viruses, all of which are enveloped and have RNA genomes. Although some types cause relatively mild illnesses, many of these viruses can cause severe, life-threatening disease. Severe illness is characterized by vascular damage and increased permeability, multiorgan failure, and shock. Confirmed cases of Ebola hemorrhagic fever have been reported in the Congo, Cote d"Ivoire, Democratic Republic of Congo, Gabon, Sudan, and Uganda. Lassa fever is caused by a virus transmitted from asymptomatically infected rodents to humans. Lassa fever is limited to rural areas of West Africa, with areas of hyperendemicity in eastern Sierra Leone, Guinea, Liberia, and Nigeria. No current treatment can cure viral hemorrhagic fevers, but the antiviral drug ribavirin can sometimes shorten the course of certain hemorrhagic fevers and help prevent complications and relapses.

Who is at Risk?
The risk for international travelers is generally considered to be low. Several cases of Lassa fever have been confirmed in international travelers. These travelers were staying or living in traditional dwellings in the countryside or in small villages; no risk has been associated with travelers who stay in hotels. Travel involving patient contact or rodent exposure is associated with increased risk. Medical personnel, researchers, and relief workers involved in the management of patients or working in disease-endemic areas should be aware of their risk and should minimize rodent exposure and use personal protective equipment to prevent health-care associated exposure.

Sources: Centers for Disease Control and Prevention, Cable News Network LP, LLLP

Possible Antibody Isolated for Ebola Virus
Ebola hemorrhagic fever is one of the most virulent diseases known to humankind. Very few pathogens are more dangerous than Ebola virus once a person is infected. There is no cure, and with a case-fatality rate of between 50 and 90 percent, depending on which strain is involved, it is one of the deadliest viruses on the planet. The virus acts quickly. It kills people in two weeks or less. Antibodies to Ebola virus appear 10 days to two weeks after the infection, which is bad timing for the infected person as the virus has more often than not run its lethal course by then. TSRI Professor Dennis Burton, Ph.D. thinks an antibody he has made might prove to provide a technology that would help.

Burton got bone marrow from two survivors and made phage display libraries from that bone marrow. Phage display is a method for selecting from billions of protein variants those that bind to a particular target. The virus is allowed to reproduce in culture, where it copiously makes new copies of itself and the antibody library. In effect, Burton reconstituted the antibody response the survivors made in Africa six months later in the laboratory. Tests carried out by Burton"s collaborators in BioSafety Level 4 laboratories have shown the antibody to be reactive against live Ebola virus in cell culture and in live models - promising results so far. Burton and his colleagues are interested in looking at the possibility of using the antibody derived from this patient as a serum that might be used to treat patients, particularly as a first-line defense for laboratory workers who accidentally receive a needle prick injury.

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A Lesson For Lassa
An acute viral illness named after the Nigerian village where it was first discovered in 1969, Lassa fever is an extraordinarily deadly disease caused by a single-stranded RNA virus. Hundreds of thousands of people a year contract Lassa fever when they come into contact with the virus, which is shed by a small rodent common to West Africa. Lassa infections can be severe, causing hemorrhagic fever and killing up to a third to a half of those infected in some outbreaks. Each year, thousands die from Lassa fever infections, but hundreds of thousands may suffer some form of deafness as a result. TSRI Professor Michael B.A. Oldstone, M.D., and his colleagues are reporting a possible mechanism for how Lassa fever virus causes hearing loss.

Oldstone has made a career of studying host-virus interactions and his work has been recognized with numerous prizes, including the J. Allyn Taylor International Prize in Medicine. A few years ago while studying a similar virus to Lassa called Lymphocytic choriomeningitis virus, or LCMV, Oldstone discovered that the receptor for Lassa fever virus and LCMV is the protein a-dystroglycan. If scientists prevent binding of the virus to that receptor, they can prevent infection from occurring. Oldstone and his colleagues report that the hearing loss that often accompanies infections with Lassa fever virus is likely related to the virus glycoprotein binding to a-dystroglycan receptors on Schwann cells in the peripheral nervous system. Lassa fever virus uses these a-dystroglycans to gain entry and then suppresses the function of the Schwann cells.

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Arenavirus Reverse Genetics
Arenaviruses, including Lassa virus, that cause severe hemorrhagic fevers in humans are also a threat as potential agents of bioterrorism. TSRI Associate Professor Juan de la Torre, Ph.D., and his colleagues developed a reverse genetics system for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) that provides a novel and powerful approach for investigating cis-acting signals and trans-acting factors involved in arenavirus RNA replication, control of gene expression, assembly, and budding and in viral interactions with cell factors.

De la Torre and his colleagues found that the arenavirus small RING finger protein Z can have a powerful inhibitory effect on viral RNA synthesis that can confer specific protection against arenavirus infection. The established LCMV reverse genetics system is an excellent platform for the investigation of novel antiviral strategies against highly pathogenic arenaviruses. The elucidation of the molecular bases that underlie the inhibitory activity of the protein Z on viral RNA synthesis and the interactions between Z and cellular factors required for virus budding may uncover new targeting strategies against arenaviruses. Likewise, the sequence and structural constraints of the arenavirus genome promoter revealed a new potential target for aminoglycoside-based antiviral drugs to combat arenaviruses.

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Arenavirus Structure, Function, And Immunology
Arenaviruses are rodent-borne agents of various diseases, including potentially lethal human hemorrhagic fevers. Recovery from Lassa virus infection usually occurs before the appearance of neutralizing antibodies, indicating that cellular immunity plays a primary role in viral clearance. To date, the role of Lassa virus-specific CD8+ T cells have not been evaluated in humans.

To facilitate studies of T-cell responses to infection with Lassa virus, TSRI Professor Michael Buchmeier, Ph.D., and his colleagues sought to identify human cytotoxic T lymphocyte epitopes, peptide sequences that in association with proteins on antigen-presenting cells are required for antigen recognition by specific cytotoxic T cells. The immunogenic epitopes identified in the study will aid in the characterization of T-cell responses to Lassa virus and in the design of arenavirus vaccines.

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