Classification and Properties of Filoviruses

Filoviruses are pleomorphic particles, appearing as long filamentous threads or as odd-shaped forms 80 nm in diameter. Unit-length particles are from 665 (Marburg) to 805 nm (Ebola). The two known filoviruses (Marburg virus and Ebola virus) are antigenically distinct and are classified in separate genera. The four subtypes of Ebola virus (Zaire, Sudan, Reston, Ivory Coast) differ from one another by up to 40% at the nucleotide level but share some common epitopes. The subtypes appear to be stable over time.

The large filovirus genome is single-stranded, nonsegmented, negative-sense RNA 19 kb in size and contains seven genes (Figure 1). An unusual coding strategy with the Ebola viruses is that the envelope glycoprotein is encoded in two reading frames and requires transcriptional editing or translational frame-shifting to be expressed. The glycoprotein makes up the viral surface spikes in the form of trimers 10 nm in length. Virions are released via budding from the plasma membrane.

Fig1. Virion structure and genome organization of filoviruses. The genome organization of Marburg virus and the Zaire subtype of Ebola virus are shown. The diagram of the virion shows the single-strand, negative-sense RNA encased in the nucleocapsid and enveloped in a lipid bilayer membrane. Structural proteins associated with the nucleocapsid are the nucleoprotein (NP), VP30, VP35, and the polymerase (L) protein. Membrane-associated proteins are the matrix protein (VP40), VP24, and the GP (peplomer glycoprotein). The genes encoding the structural proteins are identified and drawn to scale in the genome structures. Shaded areas denote the coding regions and white areas the noncoding sequences. Genes begin with a conserved transcriptional start site and end with a transcriptional stop (polyadenylation) site; adjoining genes are either separated from one another by an intergenic region (IR) or overlap one another. The site at which the additional A is added within the GP gene during transcriptional editing is indicated in the diagram of Ebola. The primary gene product of the GP gene of Ebola viruses is the SGP, a nonstructural secreted glycoprotein. At the extreme 3′ and 5′ ends of the genomes are the complementary leader and trailer sequences, respectively. (Adapted from Peters CJ, Sanchez A, Rollin PE, et al: Filoviridae: Marburg and Ebola viruses. In Fields BN, Knipe DM, Howley PM [editors-in-chief]. Fields Virology, 3rd ed. Lippincott-Raven, 1996.)

Filoviruses are highly virulent and require maximum containment facilities (Biosafety Level 4) for laboratory work. Filovirus infectivity is destroyed by heating for 30 minutes at 60°C, by ultraviolet and γ-irradiation, by lipid solvents, and by bleach and phenolic disinfectants. The natural hosts and vectors are suspected to be African fruit bats.

African Hemorrhagic Fevers (Marburg and Ebola Viruses)

Marburg and Ebola viruses are highly virulent in humans and nonhuman primates, with about half of infections ending in death. The incubation period is 3–9 days for Marburg disease and 2–21 days for Ebola. They cause similar acute diseases characterized by fever, headache, sore throat, and muscle pain followed by abdominal pain, vomiting, diarrhea, and rash, with both internal and external bleeding, often leading to shock and death. Filoviruses have a tropism for cells of the macrophage system, dendritic cells, interstitial fibroblasts, and endothelial cells. Very high titers of virus are present in many tissues, including the liver, spleen, lungs, and kidneys, and in blood and other fluids. These viruses have the highest mortality rates (25–90%) of all the viral hemorrhagic fevers.

Marburg virus disease was recognized in 1967 among laboratory workers exposed to tissues of African green monkeys (Cercopithecus aethiops) imported into Germany and Yugoslavia. Transmission from patients to medical personnel occurred, with high mortality rates. Antibody surveys have indicated that the virus is present in East Africa and causes infection in monkeys and humans. Recorded cases of the disease are rare, but outbreaks have been documented in Kenya, South Africa, Democratic Republic of the Congo, and Angola. Marburg virus can infect guinea pigs, mice, hamsters, monkeys, and various cell culture systems.

Ebola virus was discovered in 1976 when two severe epidemics of hemorrhagic fever occurred in Sudan and Zaire (now the Democratic Republic of the Congo). The outbreaks involved more than 500 cases and at least 400 deaths caused by clinical hemorrhagic fever. In each outbreak, hospital staff became infected through close and prolonged contact with patients, their blood, or their excreta. These subtypes of Ebola virus (Zaire, Sudan) are highly virulent. The mean time to death from the onset of symptoms is 7–8 days.

Subsequent outbreaks of Ebola hemorrhagic fever have occurred in Uganda (2000), the Republic of the Congo (1995, 2001, 2002, 2003, and 2018), Gabon (1994, 1996, 1997, and 2002), South Africa (1996), and Sudan (2004). Epidemics are often stopped by the institution of barrier nursing methods and training of hospital personnel, along with strict quarantine measures.

The largest known Ebola outbreak occurred in western Africa in 2014–2016, with over 28,000 cases and 11,000 deaths in Guinea, Liberia, and Sierra Leone. Intense international emergency response and quarantine measures followed, eventually containing the outbreak in June 2016. Imported cases were identified in seven other countries, with some cases of secondary transmission in the health care setting. The outbreak had major impacts on the regional economy and health care services, with up to 8% of health care workers dying from the disease, and setbacks in treatment and control of other diseases.

Filovirus infections appear to be immunosuppressive. Fatal cases often show impaired humoral immune responses. However, filovirus antibodies appear as patients recover that are detectable by ELISA. Viral antigens in serum can be detected by ELISA, providing a rapid screening test of human samples. RT-PCR can also be used on clinical specimens. One hazard to performing tests for filoviruses is that patient sera and other specimens may contain virulent virus. Tests can only be conducted under suitable biologic containment conditions. Fresh virus isolates can be cultured in cell lines such as Vero and MA-104 monkey cell lines.

It is probable that Marburg and Ebola viruses have a reservoir host, most likely the fruit bat, and become trans mitted to humans only accidentally. Monkeys are not considered to be reservoir hosts because most infected animals die too rapidly to sustain virus survival. Human infections are highly communicable to human contacts, generally by direct contact with blood, body fluids, or recently deceased victims. Typically, outbreaks of Ebola virus infection are associated with the introduction of virus into the community by one infected person followed by dissemination by person-to person spread, often within medical facilities.

Because the natural reservoirs of Marburg and Ebola viruses are still unknown, no control activities can be organized. The use of isolation facilities in hospital settings remains the most effective means of controlling Ebola disease outbreaks. Strict barrier nursing techniques should be implemented. Extreme care must be taken with infected blood, secretions, tissues, and wastes. Personnel involved in the transportation and care of nonhuman primates should be instructed about the potential hazards of handling such animals.

There are no specific antiviral therapies available although experimental antibody-based treatments are under investigation. Treatment is directed at maintaining renal function and electrolyte balance and combating hemorrhage and shock. An experimental vaccine is now available and is being tested for effectiveness as a targeted outbreak control measure.

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مواضيع ذات صلة

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Viral Serology :General Principles

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Virus detection methods: Immunodiagnosis (Antigen Detection)

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