Hantavirus

Home Properties of Hantavirus Transmission and Pathogenesis
Symptoms of Infection Diagnosis and Treatment Risk Factors and Prevention

Transmission  and Pathogenesis

Transmission of  Hantavirus infection

Spread of infection of hantaviruses between rodent hosts occurs by means of inhalation of aerosolized virus particles or by bite inoculation by an infected host. (8, 13, 14) The virus is known to be excreted in urine, feces, and saliva. (13, 14)  Rodent carriers do not show any overt clinical signs when infected with the virus, although some sub-clinical pathology can be observed upon post-mortem exam, including pulmonary septal edema and mononuclear infiltration surrounding hepatic portal triads. (14) These seem to be incidental findings, but share some similarities with pathogenesis in humans, suggesting common mechanisms of viral behaviour among rodents and humans.

 The carrier state in rodent hosts is often long lasting, and carriers may excrete virus for months to years depending on the species of hantavirus involved. (8) There may also be an age-related correlation in rodent hosts, in which young rodents seem to be susceptible to long-lasting infection, while those of several weeks are only transiently infected. (8) Transmission within host populations is horizontal (mouse to mouse) and males seem to be more affected than females, possibly due to a greater propensity to fight and contract the virus via bite wounds. (15)

Hantavirus Transmission courtesy of cdc.gov

 
Human hosts that come into contact with aerosolized particles from excreta of infected Peromyscus species carriers are at risk of contracting HPS. Transmission often occurs when excreta or mouse nests are disturbed and virus particles become aerosolized in dust and inhaled. Humans are incidental hosts of SNV and are not adapted to its presence in the body as are rodent hosts, therefore clinical disease results whenever they are infected. Hantaviruses have the potential to be transmitted through breaks in the skin, or via mucous membranes such as the conjunctiva. Ingestion may also be possible.
(8, 13, 14)  Human to human transmission has never been demonstrated in North America, although it has been potentially suggested in the case of Andes virus (ANDV) in Argentina, although the correlations are tenuous and have never been demonstrated in any other hantaviruses. (8, 16)  SNV is sensitive to drying and UV light, but often manage to survive longer than expected in the environment as they are somewhat protected from these destructive mechanisms in host excreta. (15)

 Only rodents and humans have been shown to be infected with SNV (no cases of any domestic animals or livestock contracting hantaviruses have ever been documented) however, humans should be aware of the virus in case pets bring them in contact with infected deer mice. Pet rodents should also be kept away from any wild rodents because although transmission has never occurred between the two, the potential exists for viral adaptation to new hosts. Care should be taken to exclude any sources of wild rodent contamination. (13, 17)


Pathogenesis of  Hantavirus infection

The precise pathogenesis of hantavirus is still being elucidated, although some things are known about how it leads to cellular damage. The study of the virus is made difficult by the fact that there is a lack of animal model for its study. However, the continued development of transgenic mouse lines will aid in its study, and hopefully to the development of better treatment or even prevention strategies in the future. (19, 20)

How SNV enters the cell and causes disease

Viral infection in a host begins with attachment, which in the case of hantaviruses, is assisted by the envelope glycoproteins in association with different cellular receptors which individual viruses recognize. (18) The surface glycoproteins are responsible for conferring host specificity as well as cell specificity. That is, they dictate which species of host, and which of its cells the virus can invade.

 Viral entry by endocytosis into host cells seems to be facilitated by attachment of virions to cellular receptors called β3 integrins. (18, 21, 22, 23) These are integral plasma membrane proteins on the surface of human platelets, endothelial cells, and macrophages, and are responsible for many cellular functions. (19, 21) These functions include cell-cell adhesion, immune cell recruitment, platelet aggregation, extravasation (or white blood cell migration from vessels into tissues), as well as migration of endothelial cells on extracelluar matrix proteins. (21, 24) Research has demonstrated them to mediate the cellular entry of HPS-associated hantaviruses, specifically SNV and New York-1 species. (21, 22) Since the β3 integrins play a part in regulation of vascular permeability and platelet function, they may also be related to the pathological findings of thrombocytopenia (platelet loss) and acute pulmonary edema (by increasing vessel permeability to fluid) which are findings associated with HPS in humans. (21, 23) The presence of these integrins also lends itself to specificity of humans as a susceptible host to the virus. Lung endothelial cells as well as monocyte/macrophage cells continue to be implicated as the main cellular targets in SNV infections, and disease is thought to be spread throughout the body by the blood. (24) In infected tissues, T-cell inflammatory cytokines such as tumour necrosis factor and interferon have been implicated as important mediators in the creation of inflammatory-mediated pathogenesis. (24) The N-protein of the virus seems to be a major target of the immune response, and it is possible that the virus mostly creates disease in humans by inciting aggressive inflammatory processes which damage the host cells. (24) This level of immune response may not be generated in rodent hosts who have adapted to its presence, making the level of disease asymptomatic in these hosts.


Virus attaching to lung epithelium - courtesy of apicnyc.org What Hantavirus does to WBCs - courtesy of cem.msu.edu
Virus attaching to lung epithelium
What Hantavirus does to the white blood cell



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