Laboratory Diagnostic Systems for Ebola and Marburg Hemorrhagic Fevers Developed with Recombinant Proteins

Ebola virus and Marburg virus (EBOV and MARV, respectively) of the family Filoviridae cause hemorrhagic fever with high mortality rates, sometimes reaching 50 to 90% of infected individuals, in humans and nonhuman primates (10,16,47).EBOV consists of four species, Zaire EBOV, Sudan EBOV, Ivory Coast EBOV, and Reston EBOV, which were first isolated in the Democratic Republic of Congo, Sudan, Ivory Coast, and the Philippines, respectively (47).MARV consists of one species, Lake Victoria MARV.Public health concerns about filovirus infection have increased in recent years.First, there have recently been large outbreaks of hemorrhagic fevers caused by EBOV (Ebola hemorrhagic fever [EHF]) and MARV (Marburg hemorrhagic fever [MHF]) in Africa; EHF outbreaks occurred in the Democratic Republic of Congo and Uganda in 1995 and 2000, respectively, and MHF outbreaks occurred in the Democratic Republic of Congo in 1998 -1999 and in Angola in 2004 -2005 (1, 7, 27, 56, 58-60) (1, 7, 27, 56, 58-60).Second, there is a possibility that filoviruses may be used as bioweapons.In this regard, filoviruses are classified as category A warfare agents by the U.S. government and are considered to pose a great risk to international security, along with anthrax, botulism, tularemia, and smallpox (2).As the magnitude of international trade and travel is continuously increasing, there is a significant risk that the hemorrhagic fever viruses could be introduced to virus-free countries from areas where they are endemic.Therefore, the development of laboratory diagnostic systems for EHF and MHF is an important subject even in countries without viral hemorrhagic fevers.Manipulation of infectious hemorrhagic fever viruses such as EBOV, MARV, Crimean-Congo hemorrhagic fever virus, and Lassa virus requires a biosafety level 4 (BSL-4) laboratory, which is designed for work with dangerous and exotic agents that pose a high risk of laboratory infection and life-threatening disease.However, BSL-4 laboratories are only available in a limited group of countries, such as the United States, Canada, France, the United Kingdom, Germany, South Africa, Sweden, and Russia.To get around the need for BSL-4 laboratories, recombinant viral antigens are used for immunodiagnostics.The recombi-nant proteins of these viruses have been expressed, and serological diagnostic methods have been developed using the recombinant proteins.Antigen detection systems have also been developed using recombinant antigens.In this article, recent progress in the development of diagnostic methods for EHF and MHF is reviewed.