Emory PDA Science Writers’ Magazine Infectious … · 3 | Emory Postdoc Magazine | Spring 2018 Metabolomics in the world of infectious diseases Rapidly emerging and re-emerging

1 | Emory Postdoc Magazine | Spring 2018

Emory PDA Science Writers’

Magazine

Infectious Disease Edition

Spring 2018


POSTDOC MAGAZINE

Spring 2018

Table of Contents

Metabolomic research at Emory 3

New HBV treatment 4

The next influenza outbreak 4

Antibiotic resistance 5

Studying cells with electron microscopy 6

Malaria Host-Pathogen Interaction Center 7

Detecting tuberculosis 8

Zombie deer 9

Science Writers Committee Co-Chairs

Claire Jarvis

Michelle Kim

Contributing Writers and Editors

Kim Clarke

Rebecca Crepeau

Keira Davis

Jolyn Fernandes

Claire Jarvis

Seyma Katrinli

Michelle Kim

Shariya Terrell

Alonzo Whyte

Evonne Woodson

Cover and inset photo | Emory Quad (https://odk.org/wp-

content/uploads/2015/07/emory-quad_1.jpg)

Hello and Welcome!

The Emory PDA Science Writers committee are a group

of postdocs who like to write. Some of us want to pursue

scientific writing as a career, others want to sharpen their

communication skills and practice explaining science to a

general audience. Everyone who contributed to this

newsletter has done a great job, and we’re really grateful

for their involvement.

This edition covers some intriguing research conducted at

Emory in the (broadly-defined) field of infectious diseas-

es. With our highly-regarded School of Medicine and

friendly neighbor, the Center for Disease Control and

Prevention (CDC), there is a lot to write about on this

topic.

The Science Writers committee is always looking for new

writers - either to contribute magazine articles like the

ones you’re about to read, or life/career stories for our

blog. You don’t need previous writing experience, just a

willingness to try. Email [email protected] to get in touch

with us...or any of the other postdoc committees.

We hope you enjoy reading this magazine. Thanks for

checking us out. Stay tuned for our next edition coming

out in the Fall.

Claire & Michelle, Science Writers Co-Chairs


Metabolomics in the world of infectious diseases

Rapidly emerging and re-emerging infectious diseases re-quire rapidly developing tools. It is imperative that these tools not only detect exposure but also rapidly provide strat-egies for therapeutics to combat the spread of the disease. New and improved technologies have paved the way for predicting, understanding, diagnosing, monitoring and de-veloping strategies to combat infectious disease at the sys-tems level. Metabolomics is one such high throughput tech-nology, which involves comprehensive profiling of small molecules such as amino acids, lipids, sugars and environ-mental chemicals within a cell, tissue, body fluids, or the whole infectious organism. Ultra-high resolution mass spec-trometry combined with advanced bioinformatics analysis tools are used to detect and analyze these metabolites in bio-logical samples. These metabolites could serve either as pre-dictive biomarkers that define exposure, or therapeutic bi-omarkers that fight the disease. Current investigations at Emory include utilization of this powerful technology to provide perspective and outcome to these complex diseases including parasite (malaria), bacterial (tuberculosis) and viral associated infectious disease (HIV), with an intent to ulti-mately devise therapeutic strategies.

The Malaria-Host Pathogen Interaction Center (MaHPIC), led by Dr. Mary R. Galinski, in the Division of Infectious Diseases, hosts a global collaborative project, wherein Dr. Dean P. Jones and Dr. Shuzhao Li from the Department of Medicine spearhead the Emory metabolom-ics team. The goal is to use state-of-the-art metabolic profil-ing methods to provide detailed metabolomics data for plas-ma samples collected in the course of non-human primate infections and human plasma samples from malaria endemic areas around the world.1 Detection, analysis and association between thousands of metabolites found in the blood of animals and humans infected with malaria will tremendously impact the understanding of the disease and improve global health for this parasite associated infectious disease.

The team that studies bacterial associated infectious dis-ease like tuberculosis (TB) includes Dr. Jeffrey M. Collins, in the Division of Infectious Diseases along with Dr. Thomas Ziegler and Dr. Russel R. Kempker. The aim is to use plas-ma metabolomics in the diagnosis of active tuberculosis dis-ease and identify biomarkers of the disease, treatment re-sponse and immunity.2 The Centers for Disease Control and Prevention (CDC) estimates one fourth of the world’s pop-ulation is infected with TB. Utilization of this high through-put omics technology will provide insight and public health intervention strategies for one of the world’s deadliest dis-eases.

Past studies on viral associated infectious diseases at Emory have shown that metabolomics tool is very effective in differentiating healthy HIV subjects from controls. A study published by Dr. Sushma Cribbs from the Depart-ment of Medicine showed that metabolic profiling of bron-choalveolar lavage fluid from otherwise healthy HIV infect-ed human subjects was different from the HIV-free control group, thereby providing biomarkers to predict HIV infect-ed individuals who may be at a high risk for lung infection.3

While understanding infectious diseases and their pathology is important, utilization of metabolomics tool to determine effectiveness of preventative measures against infectious diseases is equally important. The Emory Vaccine and Treatment Evaluation Unit (VTEU) is a collaborative project in the School of Medicine led by Dr. Mark J. Mulli-gan, from the Division of Infectious Diseases. This multi-million dollar project employs the utilization of metabolom-ics as one of its components to understand the immunologic responses to vaccines.4

Just like 23andme.com predicts a vast array of infor-mation based on genetic knowledge and is an easily available public avenue; metabolomics profiling to predict and pre-vent diseases may not be a far-fetched thought in the future. Precision medicine is making a way for improved strategies to combat and prevent diseases. The utilization of metabo-lomics, while still in its infancy, will soon be used to its full potential to impact individual and global health against in-fectious diseases.

Jolyn Fernandes PhD, Department of Medicine

References

(1) Metabolome-wide association study of peripheral para-sitemia in Plasmodium vivax malaria. L Gardinassi et al, Int. J. Med. Microbiol., 2017, 307, 533

(2) Plasma mycobacterium tuberculosis cell wall metabolites identify patients with multidrug resistant tuberculosis: A pilot study. J M Collins et al, 48th Annual Conference of The Union World Conference on Lung Health: Guadalajara, Mexico, 2017, 21, S75

(3) Metabolomics of bronchoalveolar lavage differentiate healthy HIV-1-infected subjects from controls. S K Cribbs et al, AIDS Res. Hum. Retroviruses, 2014, 30, 579

(4) Metabolic phenotypes of response to vaccination in hu-mans. S Li et al, Cell, 2017, 169, 862


The cure for HBV may be close with novel HBV capsid effectors

Five new 5-halogeno-heteroarylpyrimidines (HAP) analogs have recently been discovered to display anti-HBV activity in the low micro molar range. This news comes from a new-ly published article in Bioorganic & Medicinal Chemistry Letters by Emory’s own Raymond F. Schinazi, Co-Director of the Virology and Drug Discovery Core for the Emory University Center for AIDS Research (CFAR). You may also know him from his discovery of lamivudine (3TC), among the very first drugs discovered for the treatment of HIV and an active treatment strategy for HBV.

Unfortunately, still no potent cure for HBV is avail-able. Seven FDA approved HBV inhibitors can decrease viral load but cannot manage to fully eliminate HBV cccDNA which is integrated into the nucleus of hepatocytes. That’s why several HBV Capsid Assembly Effectors (CAE) have been developed over the years.

Since CAEs are promising on the way to develop a potent cure for HBV, researchers pursue the search for more effective small antiviral molecules based on their po-tential CAE. Dr. Schinazi’s group reported the discovery of the synthesis and evaluation of four new series of HAP ana-logs. They tested the anti-viral activity of more than 30 new CAE analogs of HAP-12 and GLS4 in-vitro in HepAD38

cells using real-time-PCR and also the measured cytotoxicity levels. Among them, 5 HAP-analogues were found to exert good anti-viral activity and less cytotoxicity.

Thanks to our fellow researchers, we are now 5 HAP-analogues closer to the discovery of a potent cure for HBV.

Seyma Katrinli PhD, Department of Gynecology and Obstetrics

Reference

Synthesis and antiviral evaluation of novel heteroarylpyrim-idines analogs as HBV capsid effectors. S Boucle et al, Bioorg. Med. Chem. Lett., 2017, 27, 904

Hepatitis B Virus (HBV) | Courtesy of Seyma Kantrili

Influenza coinfection…could it be the next to instigate a pandemic influenza out-break?

When RNA viruses replicate, they tend to make some mis-takes (aka mutations) along the way. In fact, it is estimated that an RNA virus makes, on average, one mistake each time it replicates…much higher than what is observed in DNA viruses. This is, in large part, due to the limited proof-reading capacity of proteins responsible for RNA replica-tion. These mistakes can either benefit the virus, making it more adapted to the host or it can be detrimental, resulting in a virus that is less fit. Either way, these mutations cause the virus to change over time (or evolve) resulting in viruses that can be quite different from parental/original strains. For RNA viruses like influenza (“flu”), different strains can infect the same cell…when this happens, entire portions of the genome can be swapped between the infecting viruses in a process called reassortment further contributing to viral evolution. But what do these mistakes and gene swappings mean for you and I?

Well…in any given flu season, there are many strains of influenza in circulation (in many different species),

yet the annual flu vaccine generally contains components from only 3-4 different strains. Thus, it is possible that you or I could become infected with multiple influenza subtypes at the same time (“coinfection”). Although the frequency of coinfection is inconsistent in the literature, there were re-ports of a spike in incidence in the 2015-2016 flu season(1, 2). Since influenza coinfection can lead to reassortment, which is responsible for generating novel strains that have fueled epidemics and pandemics in the past, it remains im-portant to define the conditions that enable reassortment to occur in vivo.

These pandemic strains arise when human and ani-mal (i.e. bird and swine) influenza viruses infect the same cell and genomic parts are swapped between the two…but what controls whether or not this can/will happen? Well, most seasonal influenza strains are generally restricted to the upper respiratory tract (i.e. trachea, upper airways, and naso-pharynx) (3), while avian and swine flu strains tend to prefer the lower respiratory tract. Thus, there are already safe-guards in place to prevent the mixing between these species-specific strains. But, we know it can happen (think Swine Flu of 2009), so the authors in a recent study sought to de-termine whether location of infection played a role in reas-sortment (4). (Continued on next page)


The researchers coinfected ferrets with two genetically dis-tinct influenza A viruses in the same anatomical site (both intranasal) versus two separate sites (intranasal and intratra-cheal). Reassortant viruses were only recovered when viruses were introduced at the same site. This study suggests that, although influenza coinfections may be more commonly detected (likely due to improvements in sequencing technol-ogy), the culprits are most likely human influenza viruses. Thus, in conclusion, although the authors did not attempt to infect with two species-specific strains at the same time in the same location to determine the likelihood of reassort-ment under these conditions, the chances that you are the breeding ground for the next influenza pandemic is relatively low thanks to the fact that animal and human influenza vi-ruses prefer different cell types (and thus different locations). And we have Mother Nature to thank for that!

Evonne Woodson PhD, Department of Microbiology & Immunology

References

(1) Influenza A(H1N1)pdm 2009 and influenza B virus co infection in hospitalized and non-hospitalized patients dur-ing the 2015-2016 epidemic season in Israel. R Pando et al, J. Clin. Virol., 2017, 88, 12

(2) Co-infection with influenza viruses and influenza-like virus during the 2015/2016 epidemic season. K Szymanski et al, Adv. Exp. Med. Biol., 2017, 968, 7

(3) Live imaging of influenza infection of the trachea reveals dynamic regulation of CD8+ T cell motility by antigen. K Lambert Emo et al, PLoS Pathog., 2016, 12, 1005881

(4) Influenza A virus reassortment is limited by anatomical compartmentalization following co-infection via distinct routes. M Richard et al, J. Virol., 2018, 92, e02063

Resistance to a ‘last resort’ antibiotic seen in mice

Carbapenemase-resistant Enterobacteriaceae (CRE) infections are a significant public health concern due to high mortality rates and a shortage of efficacious treatment options. Dr. David Weiss, Director of the Emory Antibiotic Resistance Center, studies how CRE become resistant to polymyxin antibiotics, which is a drug of last resort against these highly resistant bacteria.

Through the Multi-site Gram-Negative Surveillance Initiative (MuGSI), which operates under the auspices of the CDC’s Emerging Infections Program, Dr. Weiss’ lab characterized two distinct clinical isolates of carbapenemase-resistant Klebsiella pneumoniae (CRKP) collected at hospitals located in Atlanta, GA. Their recent publication in the March/April 2018 edition of mBio has garnered national attention. It was the first report to demonstrate that CRKP strains isolated within the United States exhibited hetero-resistance, or a difference in sensitivity, to the last-line poly-myxin antibiotic colistin amongst the CRKP strains.

The isolated heteroresistant strains of CRKP har-bored a stable subpopulation (as low as 1 in 1,000,000) of colistin-resistant bacteria that exhibited a significant and reversible growth advantage over colistin-susceptible bacte-ria in the presence, but not in the absence, of colistin. Au-thors utilized robust gene sequencing techniques to confirm that the two populations of bacteria were identical at the genetic level, which is a hallmark of heteroresistance. Analy-sis of gene expression patterns revealed changes in two pre-viously identified resistance genes that were likely to be re-sponsible for the observed differences between resistant and susceptible bacteria.

Lastly, mice were treated with a lethal dose of the clinical CRKP isolates that were either colistin-

heteroresistant or colistin-susceptible. The colistin-heteroresistant mice did not respond to colistin treatment and rapidly succumbed to the infection while colistin-susceptible mice achieved a 100% survival rate after treat-ment with colistin.

This report underscores the dangerous disguise of heteroresistance. Only one out of three standard clinical laboratory tests used in this study to evaluate antibiotic sus-ceptibility positively identified colistin resistance in both CRKP isolates. The authors concluded that colistin-heteroresistance could be responsible for treatment failure of CRKP and other related CRE infections in clinical set-tings and stressed the urgency for more sensitive diagnostics that will accurately identify antibiotic resistance and ulti-mately improve patient outcomes.

Shariya Terrell PhD, Department of Microbiology & Immunology

Reference

Carbapenem-resistant Klebsiella pneumoniae exhibiting clinical-ly undetected colistin heteroresistance leads to treatment failure in a murine model of infection. V I Band et al, mBio, 2018, 9, e02448

Colistin | https://www.webmd.com/drugs/2/drug-8761/

colistin-colistimethate-sodium-injection/details


Direct correlation of cell and structural bi-ology using cryo-correlative light and elec-tron microscopy

Elucidating the structure-function relationship of a pathogen and its interactions with a host cell can provide valuable in-sight into the mechanism of infection and progression of the virus life cycle, thus guiding the development of vaccines and treatments. In recent years, cryo-electron microscopy (cryo-EM) has become a leading technique in providing high-resolution structural data of biological samples. Since speci-mens prepared for cryo-EM are quickly converted from liq-uid to solid phase without the formation of ice crystals (i.e. vitrified), macromolecular interactions are preserved provid-ing a precise snapshot of the native state within a cell. How-ever, locating these interactions during cryo-EM analysis is extremely challenging. To resolve this, a new method called correlative light and electron microscopy (CLEM) was devel-oped.

CLEM combines the advantages of fluorescence microscopy (e.g. ability to monitor processes within the cell over time, fluorescent labeling of specific proteins to observe interactions) with high-resolution imaging characteristic of cryo-electron tomography (cryo-ET) to observe biological processes at the cellular level, while also obtaining structural data, respectively.1-2 In addition, this approach reduces the amount of cell processing, such as chemical fixation, re-quired for data collection. In a recent study, Wright and co-workers analyze virus infected or transfected mammalian cells using their new cryo-CLEM protocol.3 First, the au-thors perform cryo-fluorescence light microscopy (cryo-fLM) to identify a region of interest within a cell followed by cryo-TEM at low magnification. The coordinates of each image, fLM and TEM, are registered to ensure that the re-gions of interest identified from fLM can be found when

switching to high magnification EM. Finally, cryo-ET is per-formed to collect 3-dimensional structural data. Using this cryo-CLEM approach, Wright and co-workers were able to visualize tethers between HIV-1 virions and the host-cell membrane.4

Although there are many advantages to this new technology, the authors do point out two main disadvantages of this imaging technique. Specifically, samples need to be less than 750 nm thick. This limit can make it challenging to analyze thicker regions of whole cells, such as regions around the nucleus, requiring the addition of alternative techniques. The second limitation is the resolution limit of traditional light microscopy (200 nm), but future advances in super-resolution cryo-light microscopy should help mitigate this problem. Despite these factors, cryo-CLEM is an improve-ment to traditional methods and will prove to be a valuable resource in many areas of structural cell biology, including elucidating processes of virus life cycles.

Kim Clarke PhD, Department of Chemistry

References

(1) Correlative microscopy: bridging the gap between fluo-rescence light microscopy and cryo-electron tomography. A Sartori et al, J. Struct. Biol., 2007, 160, 135

(2) Recent advances in retroviruses via cryo-electron microsco-py. J Mak, A deMarco, Retrovirology, 2018, 15, 23

(3) Correlated fluorescence microscopy and cryo-electron tomography of virus-infected or transfected mammalian cells. C M Hampton et al, Nat. Protoc., 2017, 12, 150

(4) Three-dimensional structural characterization of HIV-1 tethered to human cells. J D Strauss et al, J. Virol., 2016, 90, 1507

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Bite to the future – studying malaria at Emory

What do time travel, self-repairing homes and Emory’s ma-laria research program have in common? The answer: they’re all funded by the US military.

The Defense Advanced Research Project Agency (DARPA) is an agency within the Department of Defense, one that focuses on adapting emerging technologies for the military. It awarded $6.4 million to several Atlanta institu-tions in 2016 as part of a 3-year contract into understanding malaria resilience.

Malaria research at Emory is focused around the Malaria Host-Pathogen Interaction Center (MaHPIC, pro-nounced may-pick). MaHPIC was established in 2012 with a 5-year NIH contract. The Center uses systems biology to gather large quantities of data about the progression of ma-larial infections. Its multidisciplinary investigators come from Emory, Georgia Tech, and the Center for Disease Control (CDC) as well as from universities around the coun-try. Mary Galinski was principal investigator on the initial MaHPIC contract. In addition to her role as center director, she is a Professor of Medicine, Infectious Diseases and Global Health at Emory University.

“Using systems biology approaches we gather all kinds of data in the course of what might be a 100-day infec-tion,” she explains. This includes temperature fluctuations and the changing concentration of metabolites and parasites in the blood. “What really makes MaHPIC special in being able to bring all these different kinds of systems data togeth-er is the involvement of computational biologists and mathe-maticians who come up with computer methods and mathe-matical tools to figure out how to relate all these different kinds of diverse information.”

Being supported through a large broadly-defined contract rather than grants allows MaHPIC researchers to explore without feeling to narrow research goals. The MaHPIC website lists 36 peer-reviewed publications result-ing from the Center to date.

Postdoctoral scientist Chet Joyner works under the auspices of MaHPIC, looking at the immune responses pro-voked by malarial infection. There are several malaria species that infect humans and primates. Joyner spent his PhD look-ing at Plasmodium vivax. “When it infects you it goes to your liver like all other malaria parasites do, however unlike the others it can leave the dormant form called hypnozoite. Those hypnozoites are capable of coming out of the dormant state after you’ve been cleared of your initial infec-tion and caus what we call the relapsing infection.” He inves-tigated how relapsing and initial infections produced differ-ent immune responses from the host. The presence of non-

malaria experts at Emory helped his career almost as much as the experts. “They ask questions that are basic but you didn’t think about, and that to me is when you really start to have the great breakthroughs.”

Another benefit of MaHPIC is its proximity to the Yerkes National Primate Research Center. Most of the data generated at MaHPIC comes from studying malaria in non-human primates. Although humans and primates get infect-ed by different malaria strains and are therefore not totally comparable, Galinski sees merit in nonhuman primate ma-laria models. “We would have ongoing infections of nonhu-man primates and we would follow those monkeys as if they were human beings, but in humans you have to treat people, you cannot do infections like this.” The equivalent human parasites don’t last long enough for a comprehensive 100-day study.

What was once ‘monkey malaria’ can later become ‘human malaria’. “Another malaria species we use frequently is called Plasmodium knowlesi. And this has been known as a monkey malaria parasite that is naturally found in Southeast Asia. But it’s been making its way into the human popula-tion,” Galinski said.

The mutability of malaria is one reason why the dis-ease is not a ‘solved problem’. As Joyner explains, basic re-search into the mechanics of malaria infection is still needed.

“Malaria is one of the big 3 – HIV, TB and malaria. It gets a lot of attention,” Joyner states. “We do have fund-ing, but compared to HIV its minimal.”

Galinski agrees with this assessment. “We have to keep beating the drum, making our case because [malaria isn’t an epidemic] here in the US, but it certainly is important for people who do leave the country or when people re-turn.”

Joyner adds, “The scary thing that’s happened now is we’ve started seeing emergence of resistance - in Southeast Asia what they’ve called ‘superbug malaria’ that are resistant to many of the frontline treatments.” (Continued on next page)

Long-tailed macaques have evolved resistance to the P. knowlesi

malaria strain | https://en.wikipedia.org/wiki/Crab-

eating_macaque


After the NIH contract expired in 2017, MaHPIC secured new funds from DARPA and transmuted in a new direction. The current DARPA-funded project at Emory investigates ‘host-directed therapies’. As Galinksi summariz-es it: “When someone has malaria what can you give them to make them feel better and function, without necessarily kill-ing off the parasite?”

Such a therapy would allow infected military person-nel to continue performing their duties in the field. Civilians could use it to buy time and reach a clinic after the onset of symptoms.

Inspiration comes from comparing two species of monkey – rhesus and long-tailed macaques. Galinski de-

scribes how the long-tailed macaque has evolved resilience to Plasmodium knowlesi infections, whereas the rhesus monkey becomes very sick because it lacks resilience. “Put the para-site in, do all the systems biology, and see what is the differ-ence in these two monkeys?” Once that difference is charac-terized, it could be exploited as a therapeutic mechanism.

Although the facilities and institutional knowledge remains constant, there are notable ideological differences in how DARPA and the NIH direct research they fund. And it’s not just DARPA’s support of projects that appear out-landish to outsiders – efforts towards time-travel, exoskele-tons, and self-repairing houses.

“When we go to DARPA for proposals they want to fund research that is close to being ready to something that can get out there in the field. The idea is: they just want it yesterday. It doesn’t matter if it’s half-baked, or changes the next day,” Galinski explains. “They want you driving the car while you’re building it! ”

Claire L Jarvis PhD, Department of Chemistry

Reference

MaHPIC list of publications, 2018, http://www.systemsbiology.emory.edu/research/Publications/index.html

Rhesus monkeys lack resistance to P. knowelsi malaria | https://

upload.wikimedia.org/wikipedia/commons/thumb/5/5e/

Emory researchers find blood based bi-omarkers for tuberculosis

Culturing the mucous secretions for Mycobacterium tubercu-losis (Mtb) infections continues to be the standard practice of care, but can have a lead time of up to 6 weeks. A faster, more reliable method of diagnosis is critical for patient care.

Researchers at Emory University recently identified three blood based biomarkers that can distinguish between active tuberculosis (ATB) and a dormant form of tuberculo-sis known as latent tuberculosis (LTB). These biomarkers could also be used to monitor the patient’s response to treat-ment.

A cohort of patients (n=24) from the metropolitan Atlanta area were enrolled in a study to measure the bi-omarkers. Patients who were ATB-positive, HIV-negative, and harbored three Mtb-specific antigens were recruited. Us-ing flow cytometry, the researchers discovered Mtb-specific CD4+ T cells expressed immune activation markers CD38 and HLA-DR, and intracellular proliferation marker Ki-67 in

much higher frequencies for ATB. Patients with ATB who underwent TB-treatment had similar levels of these bi-omarkers to patients with LTB indicating the treatment’s ef-fectiveness.

The predictive power to determine ATB vs LTB using these biomarkers was evaluated on an independent group (n=36) in South Africa. In the blind study, investiga-tors successfully identified cases of ATB and LTB with bi-omarkers CD38 and HLA up to 95% accurately. With the proliferation Ki-67, investigators accurately identified ATB at 80% and LTB at 100% correct.

Future studies on a larger spectrum of Mtb infec-tions as well as a larger endemic TB-population are necessary to validate these biomarkers.

Michelle B Kim PhD, Department of Chemistry

Reference

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response. Adekambi et al, J. Clin. Inves-tig., 2015, 125, 1827


“No joke, there is a zombie deer epidem-ic.”

Zombie Deer. Does it sound like the title of a bad horror movie? Unfortunately, it’s not. As of March 2018, the Centers for Disease Control issued the following alert re-garding Chronic Wasting Disease (CWD); “CWD in free-ranging deer, elk and/or moose has been reported in at least 23 states in the continental United States, as well as two provinces in Canada…”1

That’s right people, CWD is worldwide! But I guess you want to know how CWD leads to zombie-like deer? CWD is a prion disease. Originally identified as “proteinaceous infectious particles” by Dr. Stanley Prus-iner, prions are misfolded proteins that can interfere with the folding of normal brain proteins thereby multiplying and spreading the infection throughout the brain. These misfolded proteins are resistant to enzymatic degradation; therefore, their accumulation within neurons eventually, leads to neurodegeneration (holes within the brain tissue). Neurodegeneration causes the infected deer to seek out brains instead of grass... just kidding, but the infected deer do behave abnormally, exhibiting elevated levels of aggres-sion, listlessness, drooling, drastic weight loss, and perhaps worse of all, lack of fear of people! These symptoms can take more than a year to manifest in the deer, and even scarier, CWD can spread among hoofed animals not just by direct contact with infected brain or muscle tissue but also through consumption of contaminated food or water! So, the CWD infection may grow even larger than the au-thorities current assumptions! Already, according to the CDC up to 25% of free-ranging deer and elk may be in-fected, while rates among captive deer have been reported as high as 79%!

Primarily the disease is spreading within the “heartland” of America and fortunately we are relatively safe from the zombie deer down here in the ATL. But is it possible that eating infected deer meat at a BBQ party this

Memorial Day, will cause you to be infected with the dead-ly prion disease? As of February 2018, the answer is a cau-tious no. According to a systematic review of over 20 em-pirical studies, Waddell, et al., found no documented cases of CWD transmission to humans.2 However… two con-trolled studies using squirrel monkeys, and several others using in vitro models did provide evidence for CWD prion proteins infecting primate cells. The researchers concluded that if CWD were to infect humans it could have an incu-bation period of decades. So folks, it’s possible that we are on the verge of witnessing Corporeal Walking Dead, a CWD epidemic in humans which would undoubtedly be more exciting then seasons 7 & 8 of the Walking Dead.

Alonzo Whyte PhD, Department of Pediatrics

References

(1) Centers for Disease Control, 2018, https://www.cdc.gov/prions/cwd/occurrence.html

(2) Current evidence on transmissibility of chronic wasting disease prions to humans - a systematic review. L Waddell et al, Transbound. Emerg. Dis., 2018, 65, 37

Zombie Deer ! | http://en.goodtimes.my/wp-

content/uploads/2018/02/deer-4-300x158.jpg

Estimated spread of CWD throughout the US. |

https://www.cdc.gov/prions/cwd/occurrence.html

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Emory PDA Science Writers’ Magazine Infectious … · 3 | Emory Postdoc Magazine | Spring 2018 Metabolomics in the world of infectious diseases Rapidly emerging and re-emerging