Study on Suppressive Effect of Anthropogenic Stress and Regulation of Hantavirus Persistence in

Rodents

Presented By:Abdullah Mahmud-Al-Rafat

Supervised By: Mahbub-E-SobhaniAssociate professorBiotechnology and Genetic Engineering DisciplineKhulna University.

Hantavirus and Rodent• Hantavirus is a deadly zoonotic viruses harbored by rodents.

• Hantaviruses show no clinical symptoms in reservoir rodents while humans, who come into contact with hantavirus-infected rodent excretions like faeces, urine or saliva, most commonly through inhalation of aerosols, become infected with hantavirus and start to develop clinical symptoms.

• Average mortality rate is 60%.

Anthropogenic stress• Anthropogenic changes, caused by man-made disturbances of the natural

environment, result in anthropogenic stresses to wildlife.

• Events responsible for anthropogenic stress is known as ‘Anthropogenic stressors’.

• This has been identified as a key factor for the recent repeated breakout of emerging infectious diseases from wildlife reservoirs.

• Neither the impact of such stressors nor their mechanism of action has been studied in details.

Anthropogenic Stress and Hantavirus Outbreaks

• Rodents that are exposed to chronic anthropogenic stress are reported to have elevated levels of glucocorticoid (GC), a major immunosuppressive hormone.

• GCs are responsible for reducing resistance and elevating tolerance, thereby supporting viral persistence.

• Chronic stress is responsible for increasing an animal’s susceptibility to infection.

Anthropogenic Stress and Hantavirus Outbreaks

• Most hantavirus outbreaks occur in those areas where the environment is extensively disturbed due to anthropogenic changes and rodents experience chronic anthropogenic stresses.

• This is why outbreaks of viral infections are more prevalent in urban animals than in their rural counterparts.

• At present, rodents are known to be a reservoir to more than 60 human-infecting viruses.

Most Common Anthropogenic Stressors

1. Deforestation2. Urbanization3. Noise 4. Artificial Lighting 5. Electromagnetic Fields

Deforestation and Urbanization• Effects: Habitat fragmentation, food scarcity,

high food competition, dense colony which act as chronic stressors.

• Loss of biodiversity increase pathogen transmission risks.

• Results in rapid morphological changes, lower immunity, elevated level of stress hormone GCs.

• Positive relationship found between anthropogenic changes and hantavirus disease emergence.

Manhattan City, before and after urbanizationSource: National Geographic

Noise Effect• Significant levels of physiological changes occur in

those rodents that are exposed to noise while no such changes are observed in rodents in natural environment.

• Several experiments showed, noise exposed rodents express elevated level of corticosterone, immune alteration, a decrease in reproductive function, reduced body weight and reduced gastric secretion.

• Reduced humoral immune response and phagocytic activity and also a decreased number of T lymphocytes.

Artificial Lighting• Suppress the rhythmicity of circadian activity, body temperature

and initiate sleep deprivation in rodents.

• Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and alter the consequent stress response, increase concentrations of plasma corticosterone.

• Constant light or light-light cycle alter the balance of several hormones, including prolactin, GC, adrenocorticotropic-releasing hormone, corticotrophin-releasing hormone, serotonin and melatonin.

• Suppress immunostimulation.

• Suppress of cell-mediated and humoral immune responses in rodents.

Electromagnetic Field

• Exposure of rodents to ELF-EMF promotes chronic stress and triggers activation of the HPA axis.

• Long-term exposure to ELF-EMF induces elevated levels of plasma corticosterone and depressive-like behaviours in rodents.

• Suppression of cellular immunity.

Outcomes of Chronic Anthropogenic Stressors in Rodents and Hantavirus Emergence

Elevated concentration of Glucocorticoids (GCs)

Urbanization

Deforestation

Electromagnetic Field

Chronically stressed rodent

Increased in blood glucose

Altered behavior

Reduced growthReduced reproduction

Modulated immune system

Susceptible to viral infectionDense rodent colony in same ecological community

Interspecies or intraspecies wounding

Increased migration to areas of human habitation

Hantavirus transmission routes

Artificial lighting

Modes of Anthropogenic Stressors

Noise effect

Mechanism of Hantavirus Persistence in Rodents and Involvement of Stress Hormone

• Humans showed excessive pro-inflammatory and antiviral responses.

• Rodents showed reduced pro-inflammatory and antiviral responses and increased regulatory responses in persistent hantavirus infection.

• Glucocorticoid (GC) suppress this antiviral response and increase the regulatory responses of rodent, thereby establish hantavirus persistence.

M1 Macrophage

Macrophage

M2 Macrophage

Th2Th1

IL-5IL-4

IL-10IL-13

IFN-ϒIL-2

TNF-α

NK Cell

IFN-ϒ

CD8+ Cell

TNF-α

IL-10TGF-β

TNF-α

TH1 Cytokines

Dendritic Cell

IFN-αTNF-α

Tolerogenic DCIL-10

TGF-β

Hantavirus clearance

Hantavirus persistence

Hantavirus

GC mediated suppression

GC mediated activationDown regulation

Treg Cell

Unplanned and unorganized urbanization

Increased destruction of natural environment

Increased susceptibility of wild species to infection

Unwanted interaction of human with infected wild species

Increased emergence rate of infectious disease

Stressed wild species

•Deep Insights on natural phenomenon of reservoir-host survival can lead to future therapeutic approaches.

•Future research should be focused on systemic and holistic approaches.

•Age of uncontrolled urbanization and technology has introduced the age of uncountable diseases.

Thank you all…

For more details, please read our full version manuscript through this link

http://pubs.sciepub.com/ajidm/3/2/4/