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Challenges to Initial Identification of Etiologic Agents

The discovery of the novel hantaviruses has increased our knowledge about them. The findings increase the knowledge about the hantavirus host association. However, the finding challenges our current picture of their molecular evolution and origin. Despite the increasing hantaviruses described, the absence of a reverse-genetic system for observed genetic variation manipulation still hamper the virulence-mediated gene product identification, their virulence definition, and their molecular characterization. Hantavirus detection requires a broad spectrum of serological and molecular methods. The challenge in hantavirus diagnosis using serological assays is because of the short-term viremia of the virus, and the sera have a strong cross-reactivity against the nucleocapsid protein. The detection of immunoglobulin using enzyme-linked immunosorbent and immunofluorescent assays is the basis of the standard serological test for hemorrhagic fever with renal syndrome (HFRS) diagnosis confirmation (Krüger, Detlev H., Günther Schönrich, and Boris Klempa). However, in a region where there is more than a single hantavirus circulation, identification of the infecting agent during epidemiological monitoring requires cross-plague-reduction neutralization essays of serum, which are cumbersome and require containment conditions to analyze a series of hantaviruses.

Pathogen and Infectious cycle

The family of hantavirus is Bunyaviridae. The causative agent for the hantavirus is asymptomatically and persistently infected rodents. Hantaviruses do not cause any visible disease in rodents but can be transmitted to humans via rodents’ aerosols. The virus can cause two diseases: the hantavirus cardiopulmonary syndrome and the hemorrhagic fever with renal syndrome. The genus viruses are approximately 100nm with a spherical or oval shape. The single-stranded and negative-sense RNAs are the constituents of the hantavirus genome. Three types of segments that code different types of protein in the hantavirus genome (Jonsson, Colleen B., Luiz Tadeu Moraes Figueiredo, and Olli Vapalahti). For instance, the medium segment can be translated to Gc and Gn glycoprotein precursors, and the long segment can encode RdRp. Also, the open reading frame and nucleoplasmid are encoded by the short segment.

The interaction between the receptors of the cell surface integrin and viral glycoproteins helps hantaviruses to infect the host cell. The type of integrin receptor utilized during infection depends on the pathogenicity of the virus. The entry of HCP and HFRC into the host cell is facilitated by human integrin αvβ3 and αIIaβ3 expressed by endothelial and platelet cells, respectively. HCP and HFRC are responsible for hantavirus infection. A process known as clathrin-dependent endocytosis mediates the entry of hantaviruses into the host cell upon contact. The viral RdRp and the three nucleosides are dispatched into the cytoplasm of the cell immediately after internalization.

Subsequently, the synthesis of mRNA is initiated by RdRp. The mRNA formed encodes three viral proteins. The viral RNAs of the parent genome have a poly-A tail and 100 nucleotides longer than viral mRNA. “Cap snatching” is a mechanism that viral RdRp uses to initiate transcription. Cap snatching refers to a situation where a prime-and-realign mechanism occurs since the oligonucleotide used as a primer is cleaved from the transcripts of the host cell. Additionally, the cRNA synthesis assists viral RdRp in the replication of the genome. The synthesis of the negative sense viral genome requires the availability of the cRNA as a template. The maturation and assembly of the viral particles occur either on the Golgi body or the cell surface. The vesicular secretory pathway transports the virions to the cell surface. Ultimately, progeny egression occurs at the cell surface (Schmaljohn, Connie, and Brian Hjelle).

Works Cited

Jonsson, Colleen B., Luiz Tadeu Moraes Figueiredo, and Olli Vapalahti. “A global perspective on hantavirus ecology, epidemiology, and disease.” Clinical microbiology reviews 23.2 (2010): 412-441.

Krüger, Detlev H., Günther Schönrich, and Boris Klempa. “Human pathogenic hantaviruses and prevention of infection.” Human vaccines 7.6 (2011): 687-690.

Schmaljohn, Connie, and Brian Hjelle. “Hantaviruses: a global disease problem.” Emerging infectious diseases 3.2 (1997): 95.



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