Flavivirus

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A Viral Biorealm page on the family Flavivirus

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Contents

Baltimore Classification

Group IV. (+) Sense single-stranded RNA viruse

Higher Order Categories


Order:
Family:Flaviviridae
Subfamily:
Genus: Flavivirus

Description and Significance

Infection with Flavivirus may lead to Dengue(DF), or Dengue Hemorrhagic Fever (DHF). Both of these are serious disease processes that have lead to major epidemics throughout history. The first reported epidemics of Dengue occurred between 1779 and 1780 over continents as far apart as North America, Africa, and Asia [1]. Although, historically, outbreaks of dengue have been widespread, the disease process has not always been considered fatal in healthy adults [1]. Infection of Flavivirus can be deadly, however, when it leads to hemorrhagic fever or dengue shock syndrome [2].

Dengue fever continues to be a problem in some part of the world, yet no vaccines have been developed and tested on humans [1]. In addition, 50 to 100 million individuals are infected with dengue every year [3]. For this reason, it is important to continue researching this virus.


Genome Structure

Flavivirus capsids contain a single-stranded, positive-sense RNA molecule of approximately 10,700 base pairs. This genome is then surrounded by a nucleocapsid [4]. This genome consists of one open reading-frame that encodes a precursor polyprotein [4]. This polyprotein is altered both during and after translation to produce 10 proteins [5].



Virion Structure of a Flavivirus

The flavivirus is surrounded by a lipid bi-layer, which comes from the host cell. Within this bi-layer, the virion capsid exists. This capsid is composed of the capsid (C) protein that has been found to be a dimeric alpha-helical protein[6].


Reproductive Cycle of a Flavivirus in a Host Cell

Flavivirus is known to replicate in mammalian, insect, and plant cells. The virus replicates in the host cell's cytoplasm. Although the flavivirus genome mimics mRNA, it does not have a poly-A tail to help protect it from degredation. It is crucial for the virus to replicate in the cytoplasm so that it can use the ribosome of the host cell to translate it's viral RNA into a single poly-protein.

Once the poly-protein has been translated, an auto-catalytic enzyme is released that cleaves the poly-protein into three structural proteins, and seven non-structural proteins. A polymerase molecule results from this event, which then proceeds to polymerize new RNA strands for the progeny. Finally, a budding process occurs, during which the progeny are assembled and released [7].



Viral Ecology and Pathology

Invasion of the flavivirus depends on the recognition of specific glycoproteins between the host cell and the viral capsid. After infection, flavivirus glycoproteins initiate an antibody response .

References

1. Dengue Fever Fact Sheet-CDC Division of Vector-Born Infectious Diseases (DVBID). http://www.cdc.gov/ncidod/dvbid/dengue/#history Accessed on 9.16.2008

2. W. Wang, T. Sung,Y.Tsai, C. Kao,S. Chang,and C.C. King. Detection of Dengue Virus Replication in Peripheral Blood Mononuclear Cells from Dengue Virus Type 2-Infected Patients by a Reverse Transcription-Real-Time PCR Assay. Journal of Clinical Microbiology. December 2002, p. 4472-4478, Vol. 40

3. MedlinePlus: Dengue. http://www.nlm.nih.gov/medlineplus/dengue.html Accessed on 9.16.2008

4. K.C. Leitmeyer, D. W. Vaughn, D.M. Watts, C. Ramos, and R.R. Hesse. Dengue Virus Structural Differences That Correlate with Pathogenesis. Journal of Virology, June 1999, Vol. 73, 4738-4747

5. L. Markoff, X. Pang, H. Houng, B. Falgout, R. Olsen, E. Jones, and S. Polo. Derivation and Characterization of a Dengue Type 1 Host Range-Restricted Mutant Virus That Is Attenuated and Highly Immunogenic in Monkeys. Journal of Virology. Vol. 76. 3318-3328

6. C.T. Jones, L. Ma, J.W. Burgner, T.D. Groesch, C.B. Post, and R.J. Kuhn. Flavivirus Capsid Is a Dimeric Alpha-Helical Protein. Journal of Virology, June 2003, p. 7143-7149, Vol. 77, No. 12

7. Wikipedia. Flavivirus. http://en.wikipedia.org/wiki/Flavivirus Accessed on 9.16.2008

8.

Page authored for BIOL 375 Virology, September 2008

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