Phlebovirus Rift Valley Fever Virus
Classification
Viruses; ssRNA viruses; ssRNA negative-strand viruses; Bunyaviridae
Phlebovirus Rift Valley fever virus
Description and Significance
Rift Valley fever virus (RVFV) is a Phlebovirus of the Bunyaviridae family [1]. It is characterized by a three-segmented genome of negative/ambisense strand RNA in viral nucleocaspid protein and enveloped by a lipid bilayer containing two viral glycoproteins, Gn and Gc like all members of the virus family [5]. In livestock particularly cattle, sheep, and goats, it causes a large number of abortions and close to 100% mortality rates among young animals which results to a significant economic loss [3]. The virus is replicated in domestic ruminant animals resulting in high mortality and abortions [6]. Infection in humans can cause acute illness and even neurological disorders, blindness, hemorrhagic fever and thrombosis. The capability of the virus to cause major epidemics among livestock and humans make infection with this pathogen a serious public health concern.
Structure, Metabolism, and Life Cycle
RVFV is spherical shaped, enveloped virus, has a negative-sense single-stranded RNA genome made up of 3 segments [1]. The genome segments of bunyaviruses encode four structural proteins [1]. The large (L) segment encodes for the viral RNA-dependent RNA polymerase while the medium (M) segment encodes the external glycoproteins (Gn and Gc) and the nonstructural protein (NSm) [2]. The small (S) segment is ambisense, coding for the nucleoprotein (N) in the antigenomic sense and the nonstructural protein (NSs) in the genomic direction [2]. The two nonstructural proteins play a role in pathogenesis in vivo [5]. The virus is likely to have an icosahedral symmetry.
The molecular mechanism by which RVFV enters the host cell is largely unknown, however Glycoproteins Gn and Gc are required through which the virus deliver their genome into the host-cell cytoplasm [4]. This happens by fusing their envelope with a cellular membrane in order to deliver their genome segments into the cytoplasm [4]. Transcription and replication of RVFV is similar to other negative stranded RNA viruses [2]. Transcription and replication takes place in the cytoplasm of host cell [5]. During replication cycle, each segment is transcribed into mRNA which is then synthesized into complementary RNA (cRNA) or antigenome-an exact copy of the genome [2]. The cRNA represents a copy of the S ambisense segment which serves as a template for the synthesis of the NSs mRNA [2]. Since some cRNA is also present in the input virus, the virulence factor NSs is expressed immediately after the virus has entered host cell [5]. Messenger RNA synthesis is initiated through a mechanism called cap-snatching whereas the synthesis of cRNA is initiated with 5′ nucleoside triphosphates and does not require an oligonucleotide primer [2]. Ideally, cRNA is the complete copy of the vRNA whereas mRNAs terminate in the non-coding region before the 5′ end of the template for the L and M segments or in the intergenic region for the S segment [2].
For the viral life cycle, RVFV binds with an unidentified cellular receptor, enters the cell in a pH -dependent manner [6]. Once viral envelope has been removed, viral ribonucleocapsid (RNP) made of viral genomic RNA segment and N protein is released into the cytoplasm. The viral polymerase attached to RNP causes transcription resulting into synthesis of viral mRNA [6]. Primary transcription of N mRNA and NSs mRNA occur within 40 minutes of the infection from an efficient viral-sense package. The mechanism of packaging for RVFV RNP and the presence of any specific signals in the genomic RNA is not understood [6]. Replication of viral RNA occurs 1 to 2 hours after the infection and increases resulting in viral mRNAs and proteins. RNP is assembled into viral virions by interacting with the cytoplasmic proteins of Gn/Gc at the Golgi apparatus [6]. The packaging of the three RNA segments is coordinated such that M and S supports packaging of L-segment. The RVFV virion surface is highly symmetrical and is formed by 122 glycoprotein capsomers made up of 720 Gn-Gc heterodimers [6].
Ecology and Pathogenesis
RVFV is mainly transmitted by a range of mosquito species (Aedes, Anopheles, Culex, Eretmapoites, Mansonia) to animals through mosquito bites [6]. It has been shown to be transmitted by other vectors such as sandflies. The Aedes species which emerges from stagnant water during the rainy season is commonly known to transmit the disease to animals whereas Culex species are responsible to transmission of the disease to humans [1]. The NSs is the virulence factor expressed immediately after the virus has entered the host cell [5]. RVFV is experienced in many parts of sub-Saharan Africa and Arabian Peninsula. Transmission of RVFV depends on the interaction of the vector-borne mosquitos, susceptible animals and the human host [2]. Mosquitoes transmit the virus by vertical transmission to the next mosquito generation or horizontal transmission to susceptible animals which then pass it on to blood feeding mosquitoes [1]. Additionally humans get infected through contact with meat, milk and body fluids of infected animals. The disease is characterized by sudden onset of high fever, severe headache, myalgia, arthralgia, and photophobia in humans [1]. In infected animals, they develop necrotic hepatitis, hemorrhage, abortion and death rates of up to 100% in newborn animals [5].
References
[1]Wilson, M L. 2006. “Rift Valley Fever Virus Ecology and the Epidemiology of Disease Emergence” “Annals of the New York Academy of Sciences”. 70(1): 169-179. http://onlinelibrary.wiley.com.ezp2.lib.umn.edu/doi/10.1111/j.1749-6632.1994.tb19867.x/pdf
[2]Pepin, M., Bouloy, M., Bird, B H., Kemp A., Paweska, J. 2010. “Rift Valley fever virus (Bunyaviridae: Phlebovirus): an update on pathogenesis, molecular epidemiology, vectors, diagnostics and prevention”. “Veterinary Research”. 2010; 41 (6):61. http://www.ncbi.nlm.nih.gov.ezp2.lib.umn.edu/pmc/articles/PMC2896810/
[3]Bird, B., Ksiazek, T., Nichol, S. 2009. "Rift Valley fever virus". "Journal of the American Veterinary Medical Association". 234:883–893. http://avmajournals.avma.org.ezp2.lib.umn.edu/doi/full/10.2460/javma.234.7.883
[4]Dessau M., Modis, Y. 2013. "Crystal structure of glycoprotein C from Rift Valley fever virus". "Proceedings of the National Academy of Sciences USA". 110 (5):1696-701. http://www.ncbi.nlm.nih.gov/pubmed/23319635
[5]Bouloy, M., Weber, F., 2010. "Molecular Biology of Rift Valley Fever Virus". "Open Virology Journal". 4: 8–14. http://www.ncbi.nlm.nih.gov.ezp2.lib.umn.edu/pmc/articles/PMC2878978/
[6]Ikegami, T., Makino, S. 2011. "The Pathogenesis of Rift Valley Fever". "Viruses". 3(5):493-519. http://www.mdpi.com/1999-4915/3/5/493.
Author
Page authored by Sandra Ogato, student of Mandy Brosnahan, Instructor at the University of Minnesota-Twin Cities, MICB 3301/3303: Biology of Microorganisms.
