Bats, Viruses, And Their Immune Response

Common pipistrelle (Pipistrellus pipistrellus) – Credit Wikipedia

 

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For virologists and chiroptologists, an enduring mystery has been how bats are able to carry – without apparent ill effect – viruses that are normally deadly to most other mammals.

 

Long known for carrying rabies, over the past two decades we’ve discovered that bats can also harbor viruses such as Ebola, Marburg, Nipah, Hendra, and a variety of coronaviruses (including SARS). 

 

This week, in an article that appears in the Journal Science, we learn that some of the evolutionary changes that enable the bat to be the only mammal that can fly, may also help them to carry deadly viruses.

 

First a link to the Abstract (the whole paper is behind a pay wall), then excerpts from a Reuter’s news article that help flesh out the findings.

 

Published Online December 20 2012
< Science Express Index

Science DOI: 10.1126/science.1230835

• Report

Comparative Analysis of Bat Genomes Provides Insight into the Evolution of Flight and Immunity

Guojie Zhang, Christopher Cowled, Zhengli Shi, Zhiyong Huang, Kimberly A. Bishop-Lilly, Xiaodong Fang, James W. Wynne, Zhiqiang Xiong, Michelle L. Baker, Wei Zhao, Mary Tachedjian, Yabing Zhu, Peng Zhou, Xuanting Jiang, Justin Ng, Lan Yang, Lijun Wu, Jin Xiao, Yue Feng, Yuanxin Chen, Xiaoqing Sun, Yong Zhang, Glenn A. Marsh, Gary Crameri, Christopher C. Broder, Kenneth G. Frey, Lin-Fa Wang, Jun Wang

Abstract

Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world’s most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related bat species, fruit bat Pteropus alecto and insectivorous Myotis davidii.

 

We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor–κB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.

 

 

Admittedly, there is not much specificity in this abstract. 

 

Luckily, Tan Ee Lyn - Asia Health correspondent for Reuters – has an interview with the lead author -Professor Lin-Fa Wang, who reveals that some genetic changes necessary for flight may also help to moderate dangerous out-of-control immune responses known as Cytokine Storms.

Cytokines are a category of signaling molecules – proteins – that are released by immune cells that have encountered a pathogen, and are designed to alert and activate other immune cells to join in the fight against the invading pathogen.

 

Although poorly understood, the theory behind a `cytokine storm’ is this signaling process spirals out of control, resulting in an overwhelming immune response that can potentially kill the host.

 

According to Professor Lin-Fa Wang, this built-in suppression of the inflammatory (cytokine) response may be behind the bat’s unusual longevity (20 to 40 years), and their ability to `handle’ infection by normally deadly viruses.

 

 

Long-lived bats offer clues on diseases, aging

December 21, 2012 12:52 PM

HONG KONG: The bat, a reservoir for viruses like Ebola, SARS and Nipah, has for decades stumped scientists trying to figure out how it is immune to many deadly bugs but a recent study into its genes may finally shed some light, scientists said on Friday.Studying the DNA of two distant bat species,...

(Continue . . . )

 

 

In another article, this time in The Asian Scientist, the author talks about practical applications of this research, and is quoted as saying, “Our findings highlight the potential of using bats as a model system to study infection control, tumor biology, and the mechanisms of aging,”

 

 

Bats’ Immunity Against Deadly Viruses Linked To Their Ability To Fly

AsianScientist (Dec. 21, 2012) – An international team led by an infectious disease expert, Professor Lin-Fa Wang, at the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore has found that the evolution of flight in bats may have contributed to the development of a highly effective immune system, allowing bats to harbor some of the world’s deadliest viruses such as Ebola and SARS.

(Continue . . . )

 

Both news articles are worth reading in their entirety.

 

For more on cytokine storms, and how they may affect pandemic influenza mortality, you may wish to revisit some of these earlier blogs.

 

Study: Calming The Cytokine Storm

Cytokine Storm Warnings

The Baskin Influenza Pathogenesis Study

Pt. 1   Pt. 2   Pt. 3

»» Read More

Queensland: A Hendra Watch & A New Vaccine

Nipah/Hendra Virus & Fruit Bat Home Range – WHO

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Although long known to carry rabies, over the past two decades bats have increasingly been linked to emerging infectious diseases.

 

The SARS-CoV (coronavirus) outbreak of 2002-2003 – which infected roughly 8,000 people and killed nearly 800 – is undoubtedly the best known of these diseases, but is by no means the only one to emerge.

 

Genetic analysis of two recent novel coronavirus infections in the Middle East suggest (but fall short of proving) that bats may be the primary host for this virus as well (see Coronavirus `Closely Related’ To HK Bat Strains).

 

And the natural reservoir for the Ebola viruses (including Marburg) are believed to be fruit bats of the Pteropodidae family.

 

Prior to the SARS outbreak - during the 1990s – two new bat-borne viruses made headlines; Nipah and Hendra, both henipaviruses of the family Paramyxoviridae.

 

Of the two, Nipah has been the deadliest, causing outbreaks primarily in India and Bangladesh. But the virus was first discovered in April of 1999 when an outbreak occurred at a pig farm in Malaysia. 

 

During this initial outbreak, the virus jumped to local swine herds from bats, and infected more than 250 people, killing more than 100. The virus was then exported via live pigs to Singapore, where 11 more people died (see MMWR Update: Outbreak of Nipah Virus -- Malaysia and Singapore, 1999)

 

Over the past decade, Nipah has sparked a hand full of smaller outbreaks across Southern Asia with the greatest activity centered around Northern India and Bangladesh. Fruit bats (Pteropodidae) are considered the natural host of Nipah virus.

 

Perhaps most concerning has been evidence of limited nosocomial, or human-to-human transmission, of the Nipah virus (see Bangladesh: Updating The Nipah Outbreak).

 

The Nipah virus, like it’s close cousin the Hendra virus, is classified as a biosecurity level 4 (BSL-4) agent.

 

While not associated with as many human fatalities, the Hendra virus was first identified after the deaths of 13 horses and a trainer in Hendra, a suburb of Brisbane, Australia in 1994. A stable hand, who also cared for the horses, was hospitalized, but survived.

 

Another outbreak was later identified as having taken place in MacKay, 1000 km to the north of Brisbane, the previous month. Two horses died, and the owner was hospitalized several weeks later with meningitis. He recovered, but developed neurological symptoms and died 14 months later.

 

Over the past 18 years 40 outbreaks of Hendra virus – all involving horses – have been reported in Australia. Four human fatalities have been linked to the virus as well.

 

Subsequent studies have showed a high prevalence of the newly identified Hendra virus in Pteropid fruit bats (flying foxes) in the region.

 

Unlike Nipah, to date no human-to-human transmission of Hendra has been documented.

All of which brings us to the latest outbreak news, and hope for a new vaccine for horses that just became available. First stop, an update from the QLD Department of Agriculture, Fisheries, and Forestry.

 

November 2012

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Hendra virus communique no.10-5 November 2012

Hendra virus incident Ingham

Biosecurity Queensland is managing a Hendra virus incident in Ingham after a positive test result was received on Friday 2 November 2012.

 

A mare was first noticed unwell on Wednesday 31 October 2012 by her owner. She was not interested in food, had a slight nasal discharge, rapid, laboured breathing, elevated heart rate, lowered head and was unsteady on her feet.

 

A private veterinarian visited the horse and collected samples for Hendra virus testing. The horse deteriorated and went down and was euthanased on Thursday 1 November 2012.

Movement restrictions

Biosecurity Queensland has quarantined the property and undertaken tracing and risk assessments to determine susceptible animals that may have had exposure to the virus.

 

There are eight horses remaining on the property as well as dogs and cats. Several rounds of testing will be conducted on animals assessed to be at risk of being exposed to Hendra virus before the quarantine can be lifted.

 

Restrictions will apply to moving horses and horse materials on and off the infected property, and the property will be quarantined for at least one month. There are no other movement restrictions for the general Queensland horse population because of Hendra virus.

Hendra virus vaccine

A commercial pharmaceutical company has released a Hendra virus vaccine for use in horses under a Minor Use Permit. Under permit conditions, only accredited veterinarians can administer the vaccine.

 

The vaccine provides another option for the horse industry to reduce the risk of Hendra virus infection; however it is important to remember no vaccine is 100% effective and people in contact with horses need to continue to practice good biosecurity and hygiene measures even if horses are vaccinated.

 

Horse owners should discuss with their veterinarian whether vaccinating their horse is appropriate.

 

From CSIRO (Commonwealth Scientific and Industrial Research Organisation) we get more details on this newly available vaccine, via a 9 minute audio podcast & transcript.

 

Vaccine for killer Hendra virus launched

Australian horse owners and the equine industry have received an important boost in their fight against the deadly Hendra virus with the introduction of Equivac® HeV vaccine. (9:02)

• 1 November 2012

 

 

A final note, in the QLD notice above, it mentions that dogs and cats are quarantined, as well as horses. This comes about primarily because in 2011, we saw the first evidence of canine infection with the virus (see Australia: Dog Tests Positive For Hendra Virus).

 

The Queensland DAFF maintains a FAQ file on Hendra and dogs, where they write:

 

What animals have been shown to get Hendra virus?

Naturally occurring infection is limited to horses, flying foxes, humans and dogs. In animals, naturally occurring clinical disease is limited to horses.

 

Hendra virus is present in wild flying fox populations but does not appear to cause disease in them.

Laboratory studies have shown that other species including cats, guinea pigs, ferrets and pigs can develop disease when inoculated with Hendra virus in an experimental setting. Other species, including rabbits and dogs, have developed antibodies to Hendra virus in an experimental setting, but did not develop any signs of illness.

 

Although transmission from animals other than horses to humans has not been demonstrated, it is always a concern whenever a virus adapts to or jumps to a new host.

 

It not only gives the pathogen fresh opportunities to mutate and evolve, it provides another potential vector to spread the disease.

 

And when that host is a dog or a cat – animals with whom humans closely interact – it naturally serves to increases those concerns.

»» Read More

Virology Journal: Ebola Virus In Chinese Bats

Common pipistrelle (Pipistrellus pipistrellus) – Credit Wikipedia

 

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We are ten months into 2012, and so far it has been a pretty good year for Chiroptologists (scientists that study bats). 

 

While bats are often associated with diseases like rabies and histoplasmosis, over the past year we’ve seen bats linked to at least five exotic disease outbreaks around the globe and one rather unexpected discovery. 

 

In January we watched as Nipah Claimed 5 Lives in Bangladesh. Nipah, and its close cousin Hendra from Australia, are bat borne viruses that occasionally jump to humans (or other mammals) and can spark outbreaks.

 

Nipah, you may recall, was used as the basis for the fictional MEV-1 virus in the movie Contagion last year (see The Scientific Plausibility of `Contagion’).

 

 

Although no human cases are involved, last February the CDC announced the unusual discovery of a novel flu strain in little yellow-shouldered bats (Sturnira lilium) captured at two locations in Guatemala.(see A New Flu Comes Up To Bat).

While common in waterfowl, this was the first time that influenza had been detected in bats.

 

In July we saw an outbreak of Ebola Sudan in western Uganda (see Uganda: Ebola Sudan And A Timely Dispatch From The EID Journal), followed in August by an outbreak of Ebola-Bundibugyo in the Democratic Republic of the Congo (see WHO: DRC Ebola Update).

 

The natural reservoir for Ebola viruses are believed to be fruit bats of the Pteropodidae family, although the virus in humans is usually linked to the consumption of infected bushmeat (considered an intermediate host).  

 

In early September, we learned of the discovery of two cases of a novel coronavirus out of the Middle East, and once again a bat host is considered likely (see Coronavirus `Closely Related’ To HK Bat Strains).

 

And only last week, news emerged of a Marburg Virus outbreak in Uganda, which is still ongoing (WHO Update on Marburg Virus In Uganda). 

 

A close cousin to Ebola, Marburg is also believed carried by fruit bats of the Pteropodidae family, which can pass the virus on to other intermediate hosts, or directly to humans.

 

There are currently five known strains of the Ebola virus - Ebola-Zaire, Ebola-Sudan, Ebola-Reston, Ebola-Ivory Coast and Ebola-Bundibugyo – which along with the Marburg virus make up the family Filoviridae.

 

Of these, only Ebola-Reston – found in the Philippines – does not cause illness in humans. It is pathogenic in non-human primates, and has been found to infect pigs, which gives scientists some cause for concern.

 

Ebola Reston is also the only ebolavirus known to circulate outside of Africa.

 

That is . . . until now.

 

We’ve a new open access study, published this month in the Virology Journal, that has found evidence suggesting that Ebola viruses are circulating in Chinese bats, although the exact strain involved isn’t clear.

 

 

Serological evidence of ebolavirus infection in bats, China

Junfa Yuan, Yuji Zhang, Jialu Li, Yunzhi Zhang, Lin-Fa Wang and Zhengli Shi

Background

The genus Ebolavirus of the family Filoviridae currently consists of five species. All species, with the exception of Reston ebolavirus, have been found in Africa and caused severe human diseases. Bats have been implicated as reservoirs for ebolavirus. Reston ebolavirus, discovered in the Philippines, is the only ebolavirus species identified in Asia to date. Whether this virus is prevalent in China is unknown.

Findings

In this study, we developed an enzyme linked immunosorbent assay (ELISA) for ebolavirus using the recombinant nucleocapsid protein and performed sero-surveillance for the virus among Chinese bat populations. Our results revealed the presence of antibodies to ebolavirus in 32 of 843 bat sera samples and 10 of 16 were further confirmed by western blot analysis.

Conclusion

To our knowledge, this is the first report of any filovirus infection in China.

 

While researchers were able to detect cross-reactive antibodies to two types of Ebola viruses (Zaire and Reston), identification of the exact EBOV strain in China was not possible.  The author’s write:

 

The unsuccessful identification of ebolavirus-related genes in the samples is likely attributable to the often low-level of virus replication, the similarly transient nature of the infection in bats or the sequence mismatch of the PCR primers used and the target sequence of the potential unknown ebolavirus genomes.

 

 

Until the late 1990s, little thought was given to bats as reservoirs of epidemic diseases. Outbreaks of Nipah in Malaysia in 1998 - which lead to  265 cases of acute encephalitis and more than 100 deaths (cite) – put bats suddenly under the spotlight. 

 

Four years later - after the SARS outbreak in China - the SARS coronavirus was detected in horseshoe bats in China (cite), solidifying bats as important reservoirs of emerging infectious diseases. 

 

Since then scientists have discovered an increasing array of viral diseases that are carried by bats, although in many cases in isn’t clear how big a threat they actually pose to humans.

 

None of this is meant to demonize bats, as we are surrounded by a great many different hosts of zoonotic diseases.

 

Still, the CDC offers some sage advice when it comes to avoid coming in contact with bats.

 

 Take Caution When Bats Are Near

Bats play an important role in our ecosystem. However, they are also associated with diseases deadly to humans. Learn how you can stay safe when bats are near.

»» Read More