Hantaviruses are primarily rodent-borne pathogens, which have received considerable attention in recent decades due to their high mortality rate. In order to find the causes of emergence of hantavirus-associated diseases anthropogenic changes are a priority. These include urbanization, deforestation, noise pollution, light pollution and electromagnetic fields, all of which have been shown to profoundly affect rodent physiology and immunology. These transformations act as chronic stressors to rodents and cause elevated concentrations of glucocorticoids, which are a major class of immunosuppressive hormone. Glucocorticoids are responsible for altering the immune tolerance of rodents, thereby rendering them susceptible to infection. A perspective of these events affords an insight into the extent to which anthropogenic stressors are responsible for the emergence and persistence of hantaviruses in rodents. Glucocorticoids induce T regulatory (Treg) lymphocytes to reduce inflammatory and antiviral responses and to activate regulatory responses, principally through production of the cytokines interleukin-10 and transforming growth factor-β to support viral persistence. It is concluded that in order to develop a low-cost intervention strategy consideration should be given to a systemic approach to therapy of hantavirus infection. This would target both a reduction of anthropogenic stressors and a greater understanding of host-parasite interactions.

1. Study on Suppressive Effect of Anthropogenic
Stress and Regulation of Hantavirus Persistence in
Rodents
Presented By:
Abdullah Mahmud-Al-Rafat
Supervised By:
Mahbub-E-Sobhani
Associate professor
Biotechnology and Genetic Engineering Discipline
Khulna University.

2. 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%.

3. 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.

4. 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.

5. 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.

6. Most Common Anthropogenic Stressors
1. Deforestation
2. Urbanization
3. Noise
4. Artificial Lighting
5. Electromagnetic Fields

7. 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 urbanization
Source: National Geographic

8. 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.

9. 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.

10. 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.

11. Outcomes of Chronic Anthropogenic Stressors in
Rodents and Hantavirus Emergence

12. Elevated concentration of Glucocorticoids
(GCs)
Urbanization
Deforestation
Electromagnetic Field
Chronically stressed
rodent
Increased in blood glucose
Altered behavior
Reduced growth
Reduced 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

13. 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.

14. M1 Macrophage
Macrophage
M2 Macrophage
Th2
Th1
IL-5
IL-4
IL-10
IL-13
IFN-ϒ
IL-2
TNF-α
NK Cell
IFN-ϒ
CD8+ Cell
TNF-α
IL-10
TGF-β
TNF-α
TH1
Cytokines
Dendritic Cell
IFN-α
TNF-α
Tolerogenic DC
IL-10
TGF-β
Hantavirus clearance
Hantavirus persistence
Hantavirus
GC mediated suppression
GC mediated activation
Down regulation
Treg Cell

15. 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

16. •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.

17. Thank you all…
For more details, please read our full version manuscript
through this link
http://pubs.sciepub.com/ajidm/3/2/4/