Insecticides and the West Nile Virus

Just like we hear about superbacterias that build up antibiotic resistance, insecticide overuse is another major problem, and it’s allowing for selection of mosquitos that carry insecticide resistant genes. Researchers at L’Institut Pasteur in Paris observed Culex quinquefasciatus, a West Nile virus (WNV) mosquito vector to seek out an answer as to how insecticide resistance can change vector reaction with their pathogens.

When it comes to arthropod-borne viruses (aka arboviruses) such as dengue, chikungunya, Zika, and West Nile, there are no vaccines or therapy out there for them. To best avoid epidemics, controlling mosquito populations is the major intervention.

Using both insecticide resistant and insecticide susceptible Culex quinquefasciatus,  and arboviruses West Nile Virus and Rift Valley Fever Virus (RVFV) researchers  determined that for RVFV, vector competence remained the same whether the insect was resistant or not but for WNV, insecticide resistant mosquitoes transmitted the virus better than susceptible ones.

These results show that insecticide problems can quickly have other implications and suddenly become viral containment problems. If they do not already exist, protocols may need to be put in place in arbovirus susceptible areas.

More info here:

https://royalsocietypublishing.org/doi/10.1098/rspb.2018.2273

https://www.sciencedaily.com/releases/2019/01/190131113841.htm

~Brittany Stinson

The Deadly Pig Virus Making its Way West

African swine fever is freaking out U.S. pork farmers everywhere. Last year at the Iowa Pork Congress, only a handful of farmers attended a session on threat of foreign animal diseases, this January, several dozen showed up expressing concerns about the spread of African swine fever across China and now it looks like it is beginning to spread to Russia and Eastern Europe.  How and what exactly can farmers do to mitigate this threat?

The first goal is to contain the disease, that likely means euthanizing all pigs, stopping their movement and getting rid of a lot of feed and manure. It’s also possible that feed ingredients manufactured in China already contain the virus and are shipping it across the world.

What do we know about this virus? It’s a large DNA virus and can spread in several ways, as we know via pigs, but also people, latching on to and surviving on surfaces long enough to transmit to the next host. Farmers can get the virus on their shoes or it can end up in processed pork products where it can survive from weeks to months. It’s linked to hemorrhagic fever and high mortality rates in pigs, other hosts such as warthogs, bush pigs and soft ticks are infected without disease signs, making the illness even more transmissible.

This spread will no doubt mean major losses for the pork industry… although lower prices for bacon fans.

Read more at:

https://www.kunc.org/post/us-hog-farmers-see-real-threat-deadly-pig-virus-races-through-china-europe#stream/0

https://will.illinois.edu/news/story/u.s.-hog-farmers-see-a-real-threat-as-deadly-pig-virus-races-through-china

~Brittany Stinson

Megaphages target Gut Bacteria

A team of scientists from Berkeley have discovered the largest phages ever found in the human gut. These phages periodically prey on the bacteria of the gut, but are found only in humans that eat a non-Western, high-fiber, and low fat diet, such as the diet of traditional hunter-gatherer societies.

Though more virus than bacteria, macrophages have genomes that are ten times the size of normal phages and are much larger than bacteria. Their makeup makes it hard for biologists to classify them as either living or nonliving.

Specifically, scientists were interested in a particular bacteria, Prevotella, that contains snippets of megaphage DNA. This suggests that megaphage particularly target Prevotella, a bacteria that is not commonly seen in the gut microbiota of westerners. This macrophage could help  develop phage-based treatments caused by Prevotella.

Today, what is contained in the large genome of megaphages still remains a mystery. Scientists speculate that the large genomes encode proteins that prevent the bacterial host from interfering with phage replication. There is a significant amount of discovery waiting to happen in this field.

The full story can be found at  https://www.sciencedaily.com/releases/2019/01/190128161432.htm

-Angela Wang

VVN and Tick Salivary Glands- Understanding Tick Transmission

The National Institute of Health recently published a study investigating the transmission of tick-borne viruses. Tick salivary glands are intended to prevent the transmission of disease, but for some reason this is not the case with viruses. In this case the researchers examined tick-borne flaviviruses,  which include viruses that cause diseases like dengue fever, Zika, West Nile, and yellow fever (among others). 

They found that the viruses reside in specific cells in the salivary glands, and that the viral levels increase when the ticks are fed. There are also differences in levels between female and male ticks, and there is a marker for a gene that helps with infection. This gene, named VVN, is found in the tick organ where viruses are transmitted. When transcription of VVN was reduced, there was a reduced overall virus production in the tick. 

Learning more about viral tick-borne illnesses and the exact method and locale of transmission can help us understand and prevent further spread of these diseases. 

https://mbio.asm.org/content/10/1/e02628-18/figures-only

-Anja Zehfuss 1/30

Humans May Be More Susceptible to Viruses in Space

Humans have always had a fascination with the infinite space that surrounds our little planet. We dreamed of exploring it and finally made it happen in the last century. We reached the moon and now we’re working to get humans onto Mars. And while we seem to consider everything about space travel from what to eat to how to shower to how to maintain your muscle, we don’t think a lot about what’s happening at a cellular level in our bodies while up in space. Well, it turns out that we should start thinking about it more because a recent study in 2018 found that long-term spaceflight negatively affects our immune cells making us more susceptible to viruses.

 Researchers at the University of Arizona found that astronauts who were in space for six months or more had altered natural killer cells (NK cells). This type of white blood cell is responsible for recognizing and destroying virus-infected cells.

While space and space stations are sterile environments and humans are therefore not at risk of acquiring any new viruses, they are threatened by viruses laying dormant in their bodies. These viruses include any that remain in your body after initial infection, such as herpes. While herpes is not particularly life-threatening, it is still concerning that an astronaut’s immune system is compromised in space.

This study only looked at astronauts who were in spaceflight for about a year. A trip to Mars takes more than three. The question now is how compromised the immune system may become after such a long spaceflight and whether it can return to normal if the astronauts return to Earth. It also raises further questions on how viral disease might work on another planet, and whether it’s not only the lack of water and oxygen that would keep us away, but also the possibly rapid spread of disease among human Martians.

-Mailo Numazu

Source:

http://astronomy.com/news/2019/01/does-spaceflight-reduce-our-ability-to-fight-cancer-and-viruses

https://www.physiology.org/doi/pdf/10.1152/japplphysiol.00761.2018

As oncolytic viruses pick up steam, dl355 shows promise

Molecular oncologist Fumihiro Higashino and other researchers at Hokkaido University have engineered dl355, a new oncolytic virus which appears to have greater efficacy than the dl1520 oncolytic virus currently used in clinical practice. The virus was engineered from an adenovirus, which was made replication-incompetent by deletion of the E4orf6 gene for ARE-mRNA stabilization. ARE-mRNAs are known to be stable in cancer cells but rapidly degrade in healthy cells without the presence of E4orf6; by deleting E4orf6, the researchers generated a virus that could replicate only in cancer cell environments where ARE-mRNAs were naturally stable.

In work published in Oncology Reports, a dose of 100 viral particles per cell killed nearly all cancer cells within a week (as opposed to very few healthy cells), and the few cancer cell lines that survived were also killed by increasing the dosage. Testing in preclinical mouse models showed that growth of human tumors was suppressed via dl355 administration, and dl355 outperformed the dl1520 oncolytic virus currently used in the clinic. Future studies will focus on validating/building on the safety data and improving the efficacy by enhancing ARE-mRNA stabilization in cancer cells.

Read more at: https://www.sciencedaily.com/releases/2019/01/190129093709.htm

- Arjun Kumar

Anti-Ebola Monoclonal Antibody Appear Safe to Administer

Investigators at the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases have developed an investigational treatment for Ebola, and results from a Phase 1 clinical trial were recently published in The Lancet. The study generated promising safety data, with the treatment appearing both well-tolerated and easy to administer to the 18 healthy adults who participated in the trial.

An often-fatal disease caused by a group of five species in the Ebolavirus genus (part of the Filovirus family), Ebola has had a severe human and societal impact in recent years - including a major epidemic in West Africa in 2014. The NIH investigators sought to address it with mAb114, a single monoclonal antibody aimed at the Zaire ebolavirus strain. The antibody binds to the core receptor binding domain on the virus's envelope protein, preventing it from entering human cells.  All infusions of the antibody were well-tolerated, and four of the eighteen participants reported mild side effects. Absorption, distribution, and elimination of the antibody were all uniform among participants, paving the way for further trials.

Importantly, mAb114 does not require a cold chain and can be easily stored and administered, making it very useful for outbreak settings in the field. The treatment is already being offered under compassionate use to Ebola patients in the Democratic Republic of the Congo, as well as as part of a combination therapy in a Phase 2/3 clinical trial.

Read more at: https://www.sciencedaily.com/releases/2019/01/190124193403.htm

- Arjun Kumar

Can a virus be a cure for cancer? Adeno!

Researchers at Hokkaido University have engineered a version of the adenovirus capable of selectively killing cancer cells.

The virus, dl355, is a member of the Adenoviridae family and has a gene involved in viral replication, E4orf6, removed.  E4orf6 is responsible for stabilizing a type of mRNA called ARE-mRNAs in infected cells which allow for viral replication. This form of mRNA is common in stressed and cancerous cells, but quickly degrade in normal cells.

In cancerous cells, dl355 relies on the ARE-mRNA for viral replication and thus replicates faster in cancer cells than normal cells. Some viruses can be used to treat cancer because this extensive replication causes the cell to burst and die.  Scientists injected a low dose of the virus lacking E4orf6 into several types of cultured cancer cells and within seven days, most cancer cells died in contrast to normal cells which survived even beyond seven days of drug administration.

Several cancer lineages managed to survive the lose dose of dl355, but eventually died with an increase in dosage. Tumor growth suppression was also observed after dl355 was administered to mice tumors. In comparison to another adenovirus currently being used in cancer treatments, dl1520, dl355 recorded higher levels of replication in all cancer cell lines and was better at killing all but one type of cancerous cell.

-Riasoya Jodah

Read more at: https://www.sciencedaily.com/releases/2019/01/190129093709.htm

Flu Season Results are Coming in.... It's H1N1!

     The 2018-2019 influenza season is well underway, and based on the latest CDC weekly update, it looks to have peaked during the last week of December, when 7,000 positive samples of the disease were confirmed by the CDC. In 9 out of 10 CDC sentinel regions, the main culprit this year turned out to be a familiar one: H1N1, a strain of influenza A.
      H1N1 is most famous as the pathogen responsible for the devestating Spanish Influenza Pandemic of 1918, however 100 years later H1N1 is better known for causing widespread histeria than widespread death (an epidemic in 2009 comes to mind as a particular example of how the modern virus pales in comparison to its historic forebear). Despite not living up to the devestating destruction its legacy would suggest, H1N1 is still dangerous, causing tens of thousands of deaths every season it is active.
      This season does not seem to deviate from that pattern, and the specific type spreading, H1N1pdm09, is already a known killer, responsible for a handful of outbreaks during the 2016-2017 flu season that took the lives of hundreds. Additionally this specific virus seems especially nasty, having shown resistant to most antivirals in the past.
       The complete statistics from this flu season are not reported by the CDC until the late-spring at the earliest, however, with the large increases in flu vaccination this year (up about 8% on average), and pdm09 specifically included in this year's vaccines, it seems that this year's flu season could end up being a mild one, even given the spread of such a formidable virus. Only time will tell for sure if this optimism is warranted.

-J. Cole Holderman: TA Extraordinaire
https://www.cdc.gov/flu/fluvaxview/nifs-estimates-nov2018.htm
https://www.medscape.com/viewarticle/773528
https://www.cdc.gov/flu/weekly/index.htm
https://www.cdc.gov/flu/weekly/index.htm

Saving the Bees from Viral Scourge...

In the year between April 2017 and April 2018, beekeepers in the United States lost an estimated 40 percent of their colonies, a major issue for both agriculture and the environment, as bees are crucial pollinators to keep plants growing. A major cause of colony collapse in bee populations is the mite, Varroa destructor, which can transmit at least ten unique viruses to the bee colonies it invades. The viruses V. destructor transmits, including Deformed Wing Virus (DWV) and Lake Sinai Virus (LSV) cause an interesting slew of symptoms: from physical deformation of the wings, which prevents proper flying, to an inability to recall migratory paths back to the hive. Bees that leave the colonies fly off and never return. Pesticides have been used to attempt to curtail the effect of the mites on bee populations, but the parasites have rapidly developed resistance to these pesticides, and continuing to develop and deploy stronger pesticides has high economic and environmental costs. However, new research shows a promising novel approach to protecting bees from these destructive viruses. Scientists at Washington State University and the United States Department of Agriculture recently published a paper in Scientific Reports that could change the landscape of protecting bees and perhaps eventually many other species from viral disease. 

The research shows that extracts from mushrooms, in particular the mycelial tissue of common wood conk mushrooms, significantly reduced viruses in honeybee colonies. The experiments used extracts from two species of wood conks, the red reishi and the amadou, both of which have been used by humans for medicinal purposes for many thousands of years.  In the field study, a small amount of one of these mycelial extracts was added to the sugar water commonly fed to honeybees by beekeepers. Colonies fed reishi extract exhibited a 79-fold reduction in Deformed Wing Virus and a 45,000-fold reduction in Lake Sinai Virus, two major bee viruses, compared to control colonies. Though the mechanism behind these antiviral properties is not yet understood (this is the first research ever to identify a compound with antiviral properties in bees) the urgency of declining bee populations has motivated the scientists who performed this research to establish a non-profit focused on spreading this information and making mushroom-supplemented bee feeders available to the public. The goal is that all of us can help save bees by installing a bee feeder, similar to the already popular hummingbird feeder, in our own backyards.

Source: https://www.nature.com/articles/s41598-018-32194-8

~ Lisa Manzanete

Megaphages discovered via microbiome sequencing

For the first time, scientists have discovered a class of phage with over 540 kilobases per strain, as isolated from human microbiomes in Bangladesh and Tanzania, as well as African baboon and Danish pig microbiomes. These newly discovered phages (termed Megaphages) have genomes almost 10 times larger than their phage compatriots and are approximately 200 to 300 nm across. This scale makes megaphages on the same size scale as Mycoplasma bacteria and Poxviridiae viruses. 

This megaphage was isolated from a resident microbiome bacterium of Prevotella, which is capable of being pathogenic to humans. However, within the microbiome, Prevotella are found to be localized in the gut of individuals who eat common non-Western diets (including high-fiber, low-fat foods).This connection was made after it was observed that the Lak Megaphage family and Prevotella had a predator-prey population cycling relationship, where it appeared that Lak proliferation induced Prevotella cell death, and Lak phage population plateaued as Prevotella populations began growing again. Over time, this observation was shown to be consistent with the non-Western diet and their research in baboons suggest that these megaphages are becoming more and more prevalent in primate communities, especially those that prescribe to the high-fiber, low-fat diets.

Beyond the fascinating discovery detailed in the Nature Microbiology article, the discovery of megaphages may have significant impact on human disease. The authors of this paper state that the “movement of megaphages along with the movement of their host bacteria raises the possibility that disease also can move between animals and humans, and that the capacity for this is much larger with megaphage.” Given the impressively large genome of these megaphage, it is thought that they may have much wider capacities for mutation and differentiation, such that they could infect and cause disease in a wide variety of hosts, like humans. It was noted that many of the genes present in the large genome would potentially allow these phage to subvert bacterial defense mechanisms, suggesting these viruses may be highly adaptable to become pathogenic given their genomic flexibility. Further, the widespread nature of these megaphages suggest that presence in primates (as was the case for baboons and the microbiomes of humans) may propose Lak phages as a target of significant research for prevention of future disease.

~Kyle Enriquez

Sources:

https://news.berkeley.edu/2019/01/28/whopping-big-viruses-prey-on-human-gut-bacteria/

https://www.nature.com/articles/s41564-018-0338-9

Measles in Washington

Over the past few days, the state of Washington has been experiencing a measles outbreak where at least 34 cases have been confirmed. The majority of cases are located right on the border between Portland, OR and Vancouver, WA. At least 30 of the cases are confirmed to have been people who did not receive the measles vaccine and at least 24 are children between the ages of 1 and 10. The Washington government declared a state of emergency over the weekend and are hoping to use these resources to stop the spread of the highly contagious virus quickly.

Recently, there has been a increase in the number of anti-vax families. However, through this outbreak and the many more that we are seeing around the country one can hope these people realize that measles is not a virus to be messed with. Exposed people from Washington have been confirmed to have attended basketball games and even travelled in the last few days. Time will only tell if the virus will spread even further or if the increased resources will stop it now. Health officials are urging families (especially with children) to stay vigilant and look for symptoms. The recommendation is to call health officials before taking someone into a clinic as the air-borne virus can be incredibly contagious.

-Alexandra Ulmer
Domineering Ta of Doom (Cole)
Source: https://www.cnn.com/2019/01/26/health/washington-state-measles-state-of-emergency/index.html 

Antibiotics Still Prescribed by Doctors in ER for Viral Lung Infections

A new study in the Journal of the Pediatric Infectious Diseases Society highlights a concerning fact-  many doctors in the ER still prescribe infants with bronchiolitis, a viral infection, with antibiotics. Bronchiolitis is a lung infection typically caused by viruses in the pneumoviridae family and the leading cause of hospitalizatoin in infants in the United States during their first year of life, making it a common affliction whose treatment should be known. In 2006, official guidelines pivoted to recommending against antibiotic treatment in children without documented bacterial infections. Nevertheless, researchers found that between 2007 and 2015, about a quarter of children under the age of 2 afflicted by bronchiolitis received antibiotics, suggesting limited improvement compared against earlier years. 70% of children did not have a bacterial infection, rendering the antibiotics ineffective as a treatment.

Besides being wasteful, this inappropriate use of antibiotics is also harmful and can cause side effects and adverse reactions. A previous study suggests that side effects from antibiotic usage cause 70,000 emergency room visits among children in the United States. Furthermore, overuse can contribute to antibiotic-resistant bacteria, which is becoming a threat to public health. The new study suggests in the important of informing hospitals of the change in guidelines and addressing the lag between recommended behavior and clinical practice.

For more details, see here: https://www.sciencedaily.com/releases/2019/01/190117090501.htm


-Ed

Disease Doesn't Exist in a Vacuum: Ebola and Fake News in the DRC

The healthcare workers aiming to prevent the spread of the current Ebola epidemic in the Democratic Republic of the Congo are not only struggling with fighting the disease itself, but also a misinformation campaign that is hampering their efforts. The DRC had an election in December, and recently released the results. These results claim that the opposition leader, Felix Tshisekedi won the popular vote. Institutions monitoring the election, like the Roman Catholic Church monitors, claim that these results were manipulated and not a reflection of the will of the people.

The real question is- how does this manipulation of voting affect the spread of Ebola? The opposition party claimed that the previous government had actually created this strand of the Ebola virus and released it to exterminate Beni, the focal point of the beginning of the outbreak. The opposition party, now in power, is in effect accusing the prior government of releasing biological weaponry on its own people (the logic is not clear as to why this occurred, but they are running with this story). Because of this, and the spread of Ebola, they banned Beni residents from going to the polls. This caused not only a misrepresentation of votes but also more stigmatization about Ebola and the Beni/government connection, leading to an attack on an Ebola evaluation center the same day.

Fighting a disease with the lethality of Ebola is difficult even with a full arsenal of protective equipment in a developed country. In the Democratic Republic of the Congo, healthcare workers have to deal with fake news campaigns, stigma surrounding the disease, and the actualities of a disease with a death rate around 50%.

http://science.sciencemag.org/content/363/6424/213

-Anja Zehfuss, 1/27

From Human to Chimp....

Two years ago, researchers from the University of Wisconsin, Madison discovered that the virus which caused the common cold in humans was responsible for the deaths of wild chimpanzees in Uganda. Now, researchers have discovered two more human respiratory viruses among chimps in the same forest.

Between December 2016 and February 2017, the two viral outbreaks occurred within the same community of chimpanzees, creating suspicion that they were caused by the same pathogen. Although the presentation was the same and consistent with viral infection of the respiratory tract, only one of the outbreaks was fatal. The virus responsible for the lethal outbreak was metapneumovirus (MPV), while the other group of chimps that were sick but did not suffer any deaths was infected with parainfluenza 3.

In humans, MPV is rarely lethal, showing that its effects were much stronger in chimps, and though parainfluenza 3 did not cause any deaths, its mortality rate was much higher amongst the chimps relative to humans. The high virulence of parainfluenza 3 and the fact that it spread rapidly to nearly all the chimps suggested that the chimps had no immunity against it and this may have been the first time that humans transferred the virus across species. In fact, the viral genome of parainfluenza 3 found in infected chimps nearly mirrors that of the one found in humans.

While it is unclear how the virus was transferred from human to chimp, the severity of the outbreak has prompted government and conservation groups across the African continent to implement practices such as the use of masks, quarantining before forest entry and the use of hand sanitizers. As research Tony Goldberg summarizes, "All it takes is one person unwittingly carrying a 'common cold' virus to spark a deadly outbreak in apes."

-Riasoya Jodah

Read more at: <https://www.sciencedaily.com/releases/2019/01/190122104547.htm>

Hope for a New Solution to the Flu

Researchers at the London School for Tropical Medicine and London Imperial College may have had a major breakthrough in creating a way to combat the next flu pandemic. Since the 1918 outbreak that devastated millions of people, the flu has may not be sitting heavily on the minds of the masses as most of us feel protected by our yearly flu shots, but researchers are still attempting to eradicate the rapidly mutating influenza and understand the potential for another massive outbreak of a new strain. 

The flu, which mutates two viral surface proteins in order to avoid the body’s immune system and infiltrate the respiratory system: haemeglutinin (HA) and neuraminidase (NA). The researchers at the aforementioned institutions have decided to use the binding method of the virus in order to disable it. They have engineered a new form of antibody that attaches to the usual attachment sight on the virus (where it would usually attach to the sialic acid in the respiratory tract) and thus blocks it from interacting with any human cells. By targeting the sialic acid attachment sight, there is hope that this method could work for other infections such as some of the streptococci family. One thing that is really special about this new way of approaching the influenza problem is that, because the sialic acid sites are less likely to mutate at such a high frequency as the HA or NA surface proteins, this vaccine of sort could transcend multiple strains of the virus. 

For more information:

https://www.sciencedaily.com/releases/2019/01/190125120114.htm

-India Robinson

Ebola Virus Found in West African Bat

This last Thursday, Liberian health officials announced that they discovered the Ebola virus responsible for recent epidemics in a bat in Liberia. The bat was not associated with any human infections, and Liberia has not had any human cases of Ebola since 2016. The West African epidemic in Guinea, Liberia, and Sierra Leone is believed to have started with a young Guinean boy's exposure to an infected bat.

Virologist from Columbia University Simon J. Anthony's team found the genetic material from a mouth swab from a bat in the species Miniopterus inflatus. The research team came from the Liberian government, Columbia University, the University of California, Davis, and the nonprofit group EcoHealth Alliance. The research was funded by the United States Agency for International Development and is part of a project called Predict, which attempts to discover viruses before they cause epidemics.

Dr. Anthony said, "It's an incomplete study, a work in progress... It feels premature scientifically, but on the other hand, you have the public health aspect. We do have enough data to suggest to me that it is Ebola Zaire in this bat. We agree with our Liberian government partners that this information should be shared."

Educating the public about how to avoid contact with bats may work to prevent outbreaks. Still, some advice, such as avoiding caves and mines, may be easier to follow than other forms of education, such as explaining to hunters and cooks how to distinguish one bat species from another.

Lab work is still being conducted to determine whether the virus found in the bat is exactly the same strain that caused the West African epidemic. So far, the 20% of the genome that has been studied matches the epidemic strain.

Source: https://www.nytimes.com/2019/01/24/health/ebola-bat-liberia-epidemic.html


-- Caroline Aung

Oncolytic Adenovirus Therapy for Pancreatic Cancer

Pancreatic cancer is widely known as one of the most lethal forms of cancer. Patients diagnosed with Pancreatic cancer are almost always terminal and have one of the worst 5 year prognoses of all types of cancer. A defining feature of pancreatic cancer is a stroma covering which makes the tumor immunosuppressive. When a tumor begins to form, those tumor cells that carry easily identifiable antigens will be quickly killed off by the host immune system. Over time, the tumor cells that remain will not carry any distinguished antigens thus making the tumor invisible to the host immune system. What results is an effectively impenetrable tumor.

Researchers Callum Nattress and Gunnel Hallden are working with adenoviruses as possible tools to help fight pancreatic cancer. Viruses of the family adenoviridae are small, non-enveloped, double stranded DNA viruses. Importantly, adenovirus infection of cells will eventually cause the host cell to lyse. When a cancerous cell lyses, it releases tumor-associated antigens (TAAs) and damage- and pathogen-associated molecular pattern molecules (DAMPs and PAMPs). These act as the alarm signal to alert the host immune system that something is amiss in that area of the body. Also, just by infecting and destroying some tumor cells, adenoviruses can pave pathways into the tumors which can allow host immune system cells and chemotherapy drugs access to the core of the tumor.

What about non-cancerous cells? While non-cancerous cells can and will be effected by adenovirus, Nattress and Hallden have chosen to work with a very specific serotype of adenovirus - serotype 5 species C (Ad5). They have chosen this specific serotype for many reasons, one of which is that even wild type Ad5 virus causes only mild respiratory tract infections that resolve on their own in immunocompetent individuals. The virus that they will use for treatment will, of course, not be wild type Ad5, but a genetically engineered version of the virus with functions altered to best support cancer destruction. Other reasons are that Ad5 is easy to genetically engineer since it has a relatively small genome and a complete picture of all gene functions has been established.

This is exciting research because we are beginning to realize the potential for oncolytic adenovirus to work synergistically with chemotherapies, activate anti-tumor immune responses, and contribute to tumor stromal dissemination.

Advances in oncolytic adenovirus therapy for pancreatic cancer, Center for Molecular Oncology Barts Cancer Institute. 2018. C. Nattress, G. Hallden. 

Renata Starbird

New Malaria Vaccine based on CMV platform

The search for an effective malaria vaccine has been going on for many decades to treat this serious disease that caused 445000 deaths in 2016 alone. The current Malaria vaccine, Mosquirix, has only been shown to reduce transmission in children. Its effectiveness has been reducing since it has begun to be administered.

Recently a team of scientists have harnessed a cytomegalovirus (CMV) platform that is already being used in HIV and TB vaccines to attempt to create a better malaria vaccine. This attempt resulted after noticing that the T-cells produced by the vaccine exist in high concentrations in the liver, the exact spot where the malaria parasite resides after infecting humans.

This resulted in a vaccine that eliminated between 75-80% of parasites from the liver of rhesus macaques. A year later, the vaccinated nonhuman primates still had immunity against malaria, solving a common problem of the current vaccine whose efficacy diminishes over time. \

The full story can be found at https://www.news-medical.net/news/20190124/CMV-vaccine-provides-a-new-way-to-fight-malaria.aspx

~Angela, 1/24/2019

Dengue Virus to be used as Cancer Treatment

Dengue virus, one of the world’s leading causes of illness and death in the tropics, is now going to be used as a treatment for cancer.

The company, PrimeVax Immuno-Oncology, announced that it now has a worldwide license with the U.S. Army that authorizes them to use the #45AZ5 strain of dengue virus 1. Before this, the virus had only been used in vaccine testing, so this is a bold and unexpected move from PrimeVax.

The company will begin their human clinical trials of this cancer treatment by combining the dengue virus with dendritic cell therapy. This approach will destroy tumor cells from many directions: physiologically, immunologically, and apoptosis-inducing pathways. The hope is that this therapy will boost the patient’s self-immunity allowing them to battle their specific cancer. Dengue virus’ role is to break the tolerance many advanced cancer patients have for their tumor antigens by inducing high levels of cytokines.

It is also important to note that dengue virus infection isn’t dangerous with first exposure, it’s more of an annoyance. The danger comes with second exposure, which PrimeVax will take into account in their clinical trials.

For the clinical trials, PrimeVax will offer this therapy to metastatic melanoma patients after all standard therapies have failed. Once they establish an appropriate level of safety and tolerability, they will then target other cancers, such as glioblastoma and triple negative breast cancer.

We still have some waiting time before seeing any results from this novel therapy. Currently, PrimeVax is preparing their clinical trial site and once that is done, then they will begin recruiting patients.

-Mailo Numazu

Sources:

https://www.prnewswire.com/news-releases/primevax-immuno-oncology-signs-exclusive-worldwide-dengue-virus-license-with-us-army-for-cancer-treatments-300782190.html

https://www.prnewswire.com/news-releases/primevax-immuno-oncology-receives-ind-permission-from-fda-300773453.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307212/pdf/12967_2014_Article_349.pdf

https://www.infusio.org/blog/dendritic-cell-therapy-tailor-made-cancer-therapy/

Rotavirus vaccination thought to protect against type 1 diabetes in kids

Figures acquired from Australia on rotavirus vaccination reveal that cases of type I diabetes are decreased in children who have been vaccinated. Potential reasoning for this was found when Kristen Perrett and her team at Murdoch Children's Research Institute wrote a link between rotavirus infection and type I diabetes. In their research on mice, it was observed that viral infection triggered pancreatic apoptosis (cell death). Cellular apoptosis is a naturally occurring process but at abnormally high levels can have detrimental effects. 

Perrett and her team conducted their study on children who did not receive a rotavirus vaccine (prior to 2007 when the vaccine was introduced as a routine vaccine for children in Australia) and on a group of children who did receive the vaccine (after 2007). Results were that in children ages 0-4, type I diabetes cases were decreased by 14% among children who received the vaccine. 

While this is all very interesting, there are two major issues with this study as it stands. The first is that the long term effects have not been tracked. The two study groups are of very different ages and so the results that may change as the populations age cannot yet be compared. Secondly, there are many other factors that could be at play here, and the mouse study showed that infection can cause pancreatic complications, not that the vaccine prevents it. We are also missing figures on how many children normally get a rotavirus infection. 

Renata Starbird

https://www.healio.com/pediatrics/endocrinology/news/online/%7B99df92e4-380d-47f0-a8c8-172c1fd19555%7D/rotavirus-vaccination-protects-against-type-1-diabetes-in-kids