What is the Filoviridae?

Definition

The Filoviridae is a family of nonsegmented, negative-sense, ribonucleic acid
(RNA) viruses, distinguished from other members of the order Mononegavirales by
having filamentous virus particles. The two known genera, Ebola virus
and Marburg
virus, cause virulent hemorrhagic fevers in humans and other primates.

Natural Habitat and Features

The natural habitat of the Ebola virus and the Marburg virus, whose existence was unknown before 1967, has been a subject of much speculation and intense investigation. The first human cases of Marburg infection occurred in Germany but resulted from exposure to primates imported from central Africa, where sporadic direct transmission to humans also occurs. Loci of Ebola are found in Zaire, the southern Sudan, and the Ivory Coast in West Africa. Another species of Ebola, not pathogenic to humans, causes outbreaks in monkeys in the Philippines.

Extensive serological testing of likely reservoir species in affected
areas has pinpointed a common fruit bat,
Rousettus aegyptiacus, as a carrier for Marburg. Fruit bats are
strongly suspected in Ebola. They have been confirmed as carriers of
two other emergent lethal viral illnesses in the Mononegavirales order: nipah
virus infection (Southeast Asia) and hendra virus infection (Australia). In fruit
bats these viruses are either asymptomatic or cause mild illnesses.

Negative-strand RNA viruses, having penetrated a cell, serve as templates for positive strands of RNA that co-opt the cellular machinery of the cell to synthesize viral proteins. Transcription begins at a promoter site and may stop at boundaries between genes, producing positive strands coding only for certain proteins. As infection proceeds, the transcription process ignores gene boundaries and produces complete positive copies, which in turn serve as templates for the entire virus genome. Genome and proteins self-assemble into virions that bud off from the host cell membrane. Viruses of this type have high mutation rates because of an absence of proofreading ability in the enzyme that governs viral synthesis.

Pathogenicity and Clinical Significance

Members of the Filoviridae cause some of the most virulent viral illnesses
known, with mortality rates of up to 90 percent, even in modern hospital settings.
This virulence, coupled with moderate infectivity and the
potential for human-to-human transmission, make Ebola and Marburg viruses matters
of utmost concern for epidemiologists. These viruses are considered class-four hot
pathogens. Their equally devastating effect on nonhuman
primates constitutes a grave threat to rare species in central Africa. An ongoing
epidemic among lowland gorillas may lead these magnificent animals to
extinction.

Aside from Marburg virus in fruit bats, no active zoonosis attributed to Filoviridae in mammals other than primates has been identified, despite extensive searching. However, paleoviruses representing infections with genetically similar viruses occur in rodents and insectivores, and in bats, in central Africa. A paleovirus is a genetic marker, either a portion of the virus, incorporated into host deoxyribonucleic acid (DNA), or genes encoding for specific resistance, which has been passed through geologic time and can be used to trace the infection history of entire lineages of animals.

The extreme pathogenicity of Ebola and Marburg viruses dictate stringent
quarantine measures and extreme care in the protection of researchers and medical
and veterinary personnel to prevent their coming in contact with the pathogen.
Since the time of the outbreaks in Marburg and in a primate facility in Reston,
screening and quarantine procedures for the legal movement of primates used for
research have become much more rigorous, but illegal trade in monkeys from the
Eastern Hemisphere remains a concern. No endemic
infections attributable to Filoviridae are known from the
Western Hemisphere or from outside the tropics.

Identification of an active case of either disease warrants immediate isolation
of the infected person in a hospital setting. In this setting, intensive care can
be provided with minimal contact with health care providers, recent contacts can
be traced and isolated for observation, and the source of the infection can
possibly be identified. Although the prospects for finding an effective
therapeutic agent or developing a vaccine do not appear promising,
identifying the animal reservoir opens an avenue for modifying human behavior to
minimize exposure.

Drug Susceptibility

No drugs have been identified that show promise in treating either Marburg or
Ebola virus infections. One study showed some inhibition by S-adenosylhomocysteine
hydrolase inhibitors in vitro and in a lethal mouse model. Any antiviral agent
would need to be specific to the genomes and replication strategies of
negative-sense single-strand RNA viruses. No common antiviral drug is effective
against any member of the Mononegavirales.

Bibliography

Dimmock, N. J., A. J. Easton, and K. N. Leppard. Introduction to Modern Virology. 6th ed. Hoboken, N.J.: Wiley-Blackwell, 2007. A textbook for medical students and graduate students in biology, with a detailed section on the structure and replication of negative-sense single-strand RNA viruses.

Huffman, Michael, and Colin Chapman, eds. Primate Parasite Ecology: The Dynamics and Study of Host-Parasite Relationships. New York: Cambridge University Press, 2009. Contains an account of Ebola epidemics among gorillas and chimpanzees and speculations on how the disease shapes social structure.

Kahn, Alan J., ed. RNA Viruses: A Practical Approach. New York: Oxford University Press, 2000. A technical multiauthored book aimed primarily at research virologists, emphasizing genetics and molecular biology.

Mahanty, Siddhartha, and Mike Bray. “Pathogenesis of Filoviral Haemorrhagic Fevers.” The Lancet: Infectious Diseases 4 (2004): 487-498.

Norkin, Leonard. Virology: Molecular Biology and Pathogenesis. Washington, D.C.: ASM Press, 2010. Using the framework of the Baltimore classification scheme, the author provides a detailed account of virus structure and replication and of the basis for disease pathology.

Preston, Richard M. The Hot Zone. New York: Random House, 1994. The best-selling journalistic account of outbreaks of Ebola, Ebola-Reston, and Marburg viruses, with much information on pathogenesis, symptoms, and quarantine measures.