Hantavirus

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Hantavirus Properties

What is a Hantavirus?

Hantaviruses are a genus of viruses that belong to the Bunyaviridae family. There are five other genera in this group (Phlebovirus, Nairovirus, Tospovirus, Bunyavirus) but Hantavirus is the only genus of rodent-borne viruses. All other viruses of this family are transmitted by arthropod vectors. Within the Hantaviruses, there are at least 25 known antigenically different viral species, all named after the geographic location in which they were first located. Deer Mouse - courtesy of cbc.ca(1, 2, 3)

Hantaviruses do not cause symptomatic disease in their adult rodent hosts, but certain viruses have been associated with two distinctive and potentially fatal clinical syndromes in infected humans. These are hemorrhagic fever with renal syndrome (HFRS) and hantavirus (cardio-) pulmonary syndrome (HPS, or HCPS). Adapted rodent hosts serve as reservoirs of the etiologic viruses, which can then be shed and transmitted to humans in affected regions that come in contact with infected excreta. Because people in Canada and the United States are predominantly affected by HPS caused by the hantaviral species Sin Nombre Virus (SNV), this will be the main focus of later discussion. The primary reservoir host for SNV is Peromyscus maniculatus, or the deer mouse (pictured at right). (3, 4, 5)

Physical features of Hantavirus

All Hantaviruses are enveloped and are made up of negative-sensed single-stranded RNA. This means that the RNA strand encoding for viral components is in the reverse polarity (backwards). Thus, in order to replicate, the RNA must first be transcribScanning EM of Sin Nombre Virused by a virion protein called an RNA polymerase. This will generate positive-sense mRNA which can be read by host cell enzymes. The virus can then be translated in the host cell cytoplasm, which produces more viruses and eventually leads to the spread of infection within the host. (6, 7)

Viral particles are spherical, ranging in size from 80-120 nm. The virus is composed of three separate segments of RNA designated small, medium, and large based on respective sizes. The small (S) segment of RNA is responsible for encoding the nucleocapsid (N) protein which protects the genome of the virus. The mdium (M) RNA codes for the envelope glycoproteins (G1 and G2) which are produced as a single protein to start, and then cleaved cotranslationally. Finally the large RNA segment (L) is responsible for acting as a viral RNA polymerase/transcriptase (i.e., it has RNA-dependant RNA polymerase activity). All parts of the virus play a specific role in the processes of attachment/entry into the host cell, or in replicating more viral components within the host, or in aiding the spread of virus from host cell to cell.


Hantavirus Particle

Schematic drawing of a hantavirus particle. Hantaviruses are enveloped negative-strand RNA viruses. The virus particle consists 3 RNA segments, small (S), medium (M), and large (L) which code nucleocapsid (N) protein, two glycoproteins (G1 and G2) , and an RNA-dependent RNA-polymerase (RdRp), respectively. The RNA segments are associated with the N protein.

  

History of the virus

Hantaviruses first captured the attention of researchers in the 1950s during the Korean War, when approximately 3Apodemus agrarius000 soldiers were stricken with “Korean Hemorrhagic Fever”, a term now replaced by Hemorrhagic Fever with Renal Syndrome (HFRS). The disease was associated with a 5-10% mortality rate, and its severity spurred investigation into its cause. The etiological virus was detected in 1978 from Apodemus agrarius (the striped field mouse - pictured at right) and was named “Hantaan Virus” (HTNV) after the Hantan River where it was first recovered. By reacting rodent lung tissues with sera from convalescing patients, immunoflorescent reactions were observed, showing a link between the antibodies in recovering patients and the viral antigens. It was eventually classified under Bunyaviridae, but under the new genus Hantavirus because of its property of infecting rodents rather than arthropod hosts. After the discovery of HTNV, many other related viruses were isolated in Asia and Europe, and were also responsible for causing hemorrhagic fever and renal dysfunction of varying degrees (for example, Seoul, Belgrade, and Puumala viruses). (8, 9, 10)

In 1993, an outbreak of a severe pulmonary syndrome (later to be named HPS), with mortality rates 10 times higher than that seen in HFRS cases, occurred in New Mexico and other Four Corners states. The agent involved was quickly identified, andDeer Mouse dubbed Sin Nombre Virus (“no name” virus) and became the first of the hantaviruses recognized to cause disease in North America. It was assessed that climatic conditions at the time served to increase the density of nearby populations of Peromyscus maniculatus (deer mice - pictured at right) and that 30% of the mice tested seropositive for the causative virus.  (8, 9).

 Since the 1993 outbreak, SNV cases have been reported in many parts of North and South America, including Canada, with 32 affected patients being identified throughout all four of the Western Canadian Provinces leading up to September 1, 1999. HPS was made a notifiable disease across Canada on January 1, 2000, and active surveillance of the disease prior to this 1994 led to the first confirmed Canadian HPS case in British Columbia. It is thought that changes in rodent population densities in affected areas continue to have a great affect on the prevalence of cases in North America, and that rural areas tend to have the greatest burden of disease. HPS caused by SNV continues to be a concern in the Western Provinces to this day as many rodents continue to harbour the virus. (11, 12)



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