A Conversation with Steve Luby, Nipah Expert Extraordinaire

I’ve been really interested in Nipah over this past quarter and over Thanksgiving Dr. Luby was kind enough to entertain my questions. Steve Luby is cited in virtually every single paper on Nipah in Bangladesh and I’m really glad I got the chance to talk with him.

One question I had about Nipah is how to best understand the differences between the Malaysian and Bangladesh outbreaks. Nipah first came to the world’s attention in an outbreak in commercial pig farmers in Malaysia in 1998. The disease spread from there to Singapore. Nipah outbreaks have occurred every year in Bangladesh beginning in 2001.  The Nipah in Bangladesh and neighboring West Bengal have been characterized by higher rates of respiratory disease, higher mortality rates, and human-to-human transmission. Date palm sap has been implicated as an important route of virus transmission from Pteropus fruit bats to humans.

Dr. Luby had a number of really insightful things to say about the disease. He said that it’s possible that the Malaysian outbreak was just a more mild strain. However, he thought that the differences more likely have to do with differences in supportive care and the viral dose.  Bangladesh has a much poorer health care system than Malaysia. Only one or two patients have been intubated in Bangladesh despite the severity of the disease. This could easily explain the higher mortality rates in Bangladesh. Additionally, in animal studies, animals given a larger dose are more likely to develop pneumonia. People drinking date palm sap contaminated with bat feces or saliva may have been exposed to higher doses of virus.

Interestingly despite human-to-human transmission of Nipah in Bangladesh, there haven’t been any nosocomial cases. Dr. Luby highlighted how crowded government hospitals are and that family members usually do most of the care, which would explain why health workers aren’t getting sick. Ironically, hospitals are a place where disease can easily spread. 

I also wondered why Nipah has just recently become a problem. Rather than attribute the disease outbreak to a change in bat ecology, Dr. Luby thought that this was more likely a reporting issue. For example, people in Faridpur previously thought that Nipah was an outbreak of avian influenza. Bangladesh has just put in good surveillance for outbreak and response and there still isn’t surveillance in place in West Bengal, India. Luby thinks that it is likely that this zoonotic spillover has been happening for centuries. We just recently have the diagnostic tools and the surveillance in place to find it. 

By Olivia

BABO vs. ROBO

In light of the Ebola, Marburg, Hendra, Nipah, and Corona virus outbreaks, bats are an important reservoir to watch for emerging zoonotic diseases. A group of researchers recently compared bats to rodents as reservoirs of zoonotic viruses in the 2013 article “A comparison of bats and rodents as reservoirs of zoonotic viruses: Are bats special?”. The study compiled a list of viruses that have been discovered in each bat and rodent genus based on Web of Science, and compiled traits for each species, their conservation status, and phylogenetic correlation.

This study found that bats have more zoonotic viruses per species than rodents, but there are about two times as many rodent species as bat species. Each bat virus has a broader host range (4.51 bat host species per virus) than rodent viruses (2.76). Sympatry within a taxonomic order is the most important host trait associated with viral richness.  There aren’t as many sympatric overlaps in bats compared to rodents, but when it does occur, sympatry seems to be of larger consequence in bats. Bat species with smaller litter size, greater body mass, longer life spans, and more litters per year tend to be more likely hosts of zoonotic viruses.

I hadn’t previously thought about the role of torpor in facilitating disease. Apparently in big brown bats in Colorado, torpor was identified as an important factor in the perpetuation of rabies. However, this study found that torpor was negatively correlated to viral richness.

Another surprising finding was that the study did not find that phylogeny had a significant effect, but can explain “residual variation” in the models used. The authors state that phylogeny is correlated to individual variables and that it may be more important than their models suggest. I’m not sure I understand why their model wouldn’t have been able to accurately account for this variable.

Also surprising was that although bats are evolutionarily ancient mammals, rodents are evolutionarily older and more closely related to humans.  One would expect that cell receptors between humans and rodents would be more similar than cell receptors between humans and bats, which might better aid viral transmission.

The study measured the amount of interaction and removed specific species of rodents from the analyses, like Mus musculus, which has been extremely well studied in the lab, and has twice as many viruses known than for any other rodent species. How well rodents and bats have been studied would definitely impact the results of this study.

The authors conclude that their models can only account for about 43% of the variation seen zoonotic viral richness among hosts, but the majority of the variance remains unexplained. There are still a number of questions in understanding bat ecology and their ability to act as reservoirs for zoonotic disease. A lot of bat’s basic ecology remains unknown, such as the effects of pregnancy on the immune system, and roosting behavior and social structure of many species. Like all papers, this one concludes that more research needs to be done.

By Olivia

References:

(Luis A. et al. “A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special?” Proceedings of the Royal Society” 7, Apr. 2013; 280(1756): 20122753)

http://www.ncbi.nlm.nih.gov/pubmed/23378666

How Herpes Virus Alters Our DNA

A new study has revealed one of the mechanisms Herpes Simplex Virus I (HSV-1) uses to replicate effectively in a host cell.  As a reminder, HSV is a widespread virus in the U.S., which is known to cause cold sores.  A latent infection, HSV remains in the body (residing in nerve cells near the ear, lower lip, or face) even after symptoms subside, and symptoms may reemerge periodically.

The study found that HSV-1 is able to interfere in telomere functioning.  Telomeres flank the ends of chromosomes and consist of repeated DNA units that prevent a chromosome from damage during mitosis, since replication normally results in the loss of a few nucleotides on the ends of a chromosome.  HSV-1 specifically inhibits and alters TPP1, resulting in a loss of one of these repeating units.  This inhibition increases the effectiveness of HSV-1 replication.

The implications of this study are that telomeres can be targets that viruses use to more effectively replicate, and that telomere proteins such as TPP1 can have a protective effect during viral infection. Combined with the fact that telomere length has already been implicated in disease risk, this study raises the possibility that novel drugs or treatments that preserve telomere length during viral infection may hamper the ability of a virus to replicate.

Source:

http://www.medicaldaily.com/herpes-virus-manipulates-our-dna-replicate-what-those-infected-can-do-about-it-314260

--Andrew Duong

Zoonoses and Humans: Resources

This blog post may be a bit tangential to the usual viral chatter, but it’s been something I’ve been thinking about and very applicable to zoonoses, so bear with me.

I recently came across a Ted Talk by Barbara Natterson-Horowitz, a cardiologist at UCLA. (Here’s a link in case you are curious: http://www.ted.com/speakers/barbara_natterson_horowitz).  She talked about conferences she organizes based on “Zoobiquity,” and her efforts to bridge the gap between veterinarians and physicians. She thinks that there are important crossovers between humans and animals that go beyond infectious disease.

It turns out that the CDC has a somewhat different version of this idea called “One Health,” which is dedicated to looking at how the health of people is connected to the health of animals and the environment. (Here’s their homepage: http://www.cdc.gov/onehealth/). Although the similarities between veterinary and human disease have been known for a long time, (think of all those animal models that are being used to understand human disease!) the CDC created the One Health approach in 2007 in response to the risk of infectious disease. It’s impressive to see that the interrelatedness of human and animal health is recognized at this organizational level.

It also turns out that there’s also a journal called EcoHealth that looks at the crossover between ecology and health. So in summary, there are lots of folks involved in thinking about the issue of zoonoses, and it’s interesting to see that organizations like the CDC have really responded.

By Olivia

Deadly Lyssavirus Risk Factor: Aussies Lax in Reporting Bat Bites

A native Australian bat. Courtesy: Greg Wood

In Australia, many things can kill you. Among them is the Australian bat lyssavirus (ABLV), a viral zoonosis that can be transmitted from bats to humans. Since the identification of the virus in 1996, three Queenslanders have died from the lyssavirus. The common theme in each of their deaths? A significant delay in reporting exposure to bats. 

They only sought treatment after the lyssavirus incubation period, when rabies-like symptoms began. By then it is too late. As a member of the family Rhabdoviridae, ABLV is related to Rabies, another notorious virus known for its high fatality rate if vaccination is not given. Like Rabies, ABLV has a very long incubation period. Therefore, despite the lack of symptom after a bat bite or scratch, it is essential for people to seek testing.

References
http://www.brisbanetimes.com.au/queensland/relaxed-aussie-attitude-major-health-risk-from-bat-virus-expert-20141214-1270mt.html
http://access.health.qld.gov.au/hid/InfectionsandParasites/ViralInfections/australianBatLyssavirus_fs.asp

Tina

CAR T-cell Therapy: A New Kind of Immunity

Although not directly related to viruses (yet), Chimeric Antigen Receptors (CARs) may redefine how we give individuals immunity -- an important topic to discuss given how closely immunology and virology are intertwined.

CARs are a T cell therapy that involves collecting T cells from an individual patient and genetically engineering the cells so they generate special receptors -- CARs -- that enable the T cells to recognize desired antigens. After growing these engineered T cells in the laboratory, they are introduced into the patient again. And inside the body, these CAR T cells will recognize and kill any cells with the antigen of interest.

They are currently used in cancer immunotherapy, especially for childhood cancers. One trial gave T cells with CARs targeting the CD19 receptor to adults and children with leukemia and lymphoma. In this study, 27 out of 30 patients had all signs of cancer disappear and 19 of the 27 are still in remission.

Although there is much to be studied and refined in CAR T cell therapy, it certainly highlights a new way to confer immunity. By engineering the CARs in the laboratory, this therapy eliminates many of the variables and risk factors involved in vaccination, which relies on the immune system to successfully respond to a pathogen or its antigen.

References
http://www.cancer.gov/cancertopics/research-updates/2013/CAR-T-Cells
http://www.nejm.org/doi/full/10.1056/NEJMoa1215134
http://www.chop.edu/centers-programs/cancer-center/t-cell-therapy-ctl019#.VI3WZWTF-0c

Tina

The Ultimate Test: Infecting Healthy Individuals with Dengue?

At the Walter Reed Army Institute, researchers are considering using the "human challenge" model to research drugs and vaccines against dengue. Although individuals have been deliberately infected with other, less dangerous pathogens such as malaria and influenza in the past, dengue presents a much higher risk because there are no antiviral medications. With improper treatment, 20% of those infected can die. However, with proper medical care, the mortality rate is much lower than one percent. 

Why exactly are scientists willing to take the risk now? The major reason is the spread of dengue. It has increased 30-fold in the past 50 years, and has spread from just a few countries in the 1950s to over 60 countries today. There are over 22,000 deaths every year due to dengue. At this point, it is essential to conduct more research on dengue to see which strains cause illness in individuals and study them in order to give people around the world better treatment and prevention options. 

References

http://www.wsj.com/articles/dengue-fever-researchers-in-military-weigh-infecting-volunteers-1415908102?mod=U.S._newsreel_11

Tina