Tuesday, December 6, 2016

2016 Sees Worst Mumps Outbreak in Last Decade

According to the CDC, the mumps outbreaks in 2016 is worse than it has been in the last ten years. The latest Morbidity and Mortality Weekly Report, mumps cases in 2016 thus far tally 3,832, which is triple the 1,088 cases that occurred in 2015. The virus has emerged across the country, but Arkansas has a third of the total cases at 1,305. Iowa reported 645 cases, Illinois reported 377, and Indiana reported 231. There were also outbreaks in New York and Massachusetts.

University of Missouri is limiting dining hall hours and social gatherings, as it has had 128 cases this semester. All of the infected students had received the MMR vaccine. Why were they then still susceptible to the infection? The memory arm of the immune system can often need booster vaccines to bring up the level of circulating antibody for the virus, so that it can continue to mount an effective defense in case of infection. In the case of mumps vaccine, the effectiveness of the vaccine increases from the 1st dose to the second dose, from 78% to 88% effectiveness.

The easy spread of mumps among university students is likely due to the nature of dormitories, which facilitate close contact and transmission of the virus. The virus can be transmitted through respiratory droplets (coughing/sneezing/talking) or through saliva.

Mumps is caused by rubulavirus, paramyxovirus that causes swelling of the salivary glands,  as well as typical viral symptoms such as fever, fatigue, headache, and anorexia. Complications include encephalitis, aseptic meningitis, acute pancreatitis, and orchitis (testicular inflammation), Guillain-BarrĂ©, and several other complications related to inflammation.

Sources:
"Mumps: For Healthcare Providers."http://www.cdc.gov/mumps/hcp.html
"Morbidity and Mortality Weekly Report (MMWR): Notifiable Diseases and Mortality Tables." December 2, 2016. http://www.cdc.gov/mmwr/volumes/65/wr/mm6547md.htm?s_
"Mumps Outbreaks Are Worst in a Decade." December 5, 2016. http://www.wsj.com/articles/mumps-outbreaks-are-worst-in-a-decade-1480968263


Richa Wadekar

Human antibody 3E1 shows potential against Influenza A viruses

Influenza A is a member of the orthomyxoviridae family. Along with other influenza viruses, it causes from 3-5 million severe illnesses annually.  Control of influenza epidemics rely on vaccinations and some antivirals like Tamiflu, but due to antigenic drift, and hundreds of strains, they have been wickedly resistant to containment. Haemagglutinin (HA) is a glycoprotein embedded in the envelope of Influenza A, and is responsible for receptor binding and membrane fusion. Current antivirals often target the head of HA to prevent viral infection, but the head is highly variable which prevents antibody effectiveness over a wide range of the Influenza A viruses, and mutates quickly.

In a new article published in Nature, researchers chose to focus on a different part of Haemagglutinin—the stem. The stem is a more conserved area of the glycoprotein, and antibodies that target this region may have more cross-reactivity. A monoclonal antibody named 3E1 has previously shown reactivity to the HA stem region, and showed promise in blocking viral infection. In the latest research, it was confirmed that 3E1 binds to the stem of the viral glycoprotein, and it was shown that 3E1 is effective at neutralizing a wide range of H1N1 and H5N1 subtypes.

 Modeling of the antigen and its binding action demonstrate that 3E1 attaches to a highly conserved region of HA with a complementarity value comparable to other antibodies that are being investigated as weapons against Influenza A. When it binds, it prevents a conformational change in HA, which prevents it from going from a pre-fusion state to a fusion state, denying the virus access to the cell.  

Although there is still much research to be done on this antibody, it shows promise as a model for developing antibody-based therapies against pandemic flus due to the lower mutation rate of the stem, and wider range of sub strains that is can neutralize as compared to traditional antiviral therapies.

Read the full article here:

Elisa Hofmeister ‘18

BSL-4 Laboratory work

What is it like working with the most dangerous pathogens in the world?

That’s what Goats and Soda on NPR investigated this week. They interviewed Emmie de Witt, a Dutch scientist working at Rocky Mountain Laboratories in Montana.  There are only 13 operational (or being constructed) BSL-4 labs in the US, so Emmie offers a pretty rare perspective on “dangerous and exotic” microbes.  

Some of the pathogens discussed include MERS, Ebola, Nipah virus, and various types of flu (even the 1918 massively fatal strain!). Luckily, Emmie also talks about the safety precautions mandatory at all BSL-4 labs- such as non-circulating air ducts in corridors, positive-pressure protective safety suits (you have to talk via built-in radio to other scientists in the lab), showering protocols once you leave the lab, and even what type of underwear scientists have to wear…

Emmie also addresses what everyone wonders about in these types of labs- are you afraid that you might be infected and die? Fortunately, scientists generally feel safe as long as they are following safety protocols. Of course, unexpected events can happen in labs, but Emmie says that there’s a certain mindset that helps to stick to procedures and SOPs to help prevent any mistakes.

Despite the risks of working in a BSL-4 lab (and it’s downsides: uncomfortable blow-up suits, you can’t go to the bathroom or drink water once you get into the suit), Emmie still says she really likes her job. And I can totally understand why- investigating new effects of incredibly deadly viruses seems like one of the most interesting jobs around.


-Katy Graham

Sources:


Researchers identify Pandemic-level viral threats

A study at the University of Edinburgh has identified 37 viruses with the potential to cause major epidemics worldwide. All 37 have displayed transmission in humans, but have not yet caused large outbreaks of disease in the contexts in which they exist.

The viruses identified by the study were all zoonotic in nature, meaning that their transmission is largely limited to certain animals. The study's approach to the viruses was to assign to viruses one of four levels of significance to humans, corresponding each to human exposure to the virus, the incidence of infection once exposed, the potential for transmission given infection incidence, and then the potential for blow-up into a full-scale epidemic. Some viral families, like avian flus, are able to 'skip' some levels, jumping straight from exposure to human-human transmission, for example. Other, more slowly evolving viruses, may make contact with humans but, for their inability to become infective, were discounted as risks in the study.

Other parameters used to evaluate viral risk were the relatedness of virus reservoir hosts to humans, which led to a prioritization of primate viral families, viral host range, host restriction factors and host-virus coevolution. Virulence was also included both as a factor which increases the significance of viral disease, and the potential cost of a pandemic, but which also limits the ability of a virus' hosts to survive long enough to infect a great number of people.

The method of the study was previously used to report the threat of the Ebola virus strain involved in the 2014 outbreak, as well as the threat presented by the Zika virus. Despite this, the identification of the dangers these viruses posed did little to spur early precautionary measures and international coordination to monitor and respond to outbreaks of disease. While this research is certainly valuable for the understanding of the viral risks which exist, whether this value is realized depends on the ability of the international community to find ways to make practical the findings it reports.

http://www.bbc.com/news/uk-scotland-edinburgh-east-fife-38207006
http://wwwnc.cdc.gov/eid/article/22/12/16-0123_article

-Muzz Shittu

Sunday, December 4, 2016

Leftover Viruses are Implanted in our Genome

Over 8% of the human genome is made up of endogenous retroviruses (ERVs). ERVs are ancient retroviruses that inserted their own DNA into hosts, and over the course of hundreds of thousand of years of mutations they lost the ability to replicate in cells. Most of these insertions do nothing inside our genomes. However, new evidence is emerging that some ERVs “wake up” and are transcribed into RNA by the host. In 2015, researchers were studying HERVK, one of the most recent viral additions to the human genome, and discovered that it can induce viral restriction pathways in early stage embryonic cells and help protect a growing fetus against viral invaders.

HERVK is expressed during days 5-6 of embryonic development post fertilization. Its expression was discovered when researchers noted the presence of viral proteins and virus-like particles (VLPs) in the blastocyst (Fig 1).


When activated, HERVK produced as small accessory protein called Rec, which upregulates binding and exporting of viral mRNAs from the cell. Viral mRNA export likely up-regulates innate antiviral responses, which may stop other viruses from infecting the cells. Although researchers caution that there is not enough evidence to make conclusions yet, they are excited by the possibility that ancient viruses are shaping human development, and that they may even have a positive impact on the embryo as it tries to ward off other invading viruses.


Paper:

Grow, E. J., Flynn, R. A., Chavez, S. L., Bayless, N. L., Wossidlo, M., Wesche, D. J., . . . Wysocka, J. (2015). Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells. Nature, 522(7555), 221-225. doi:10.1038/nature14308

New York Times article:




Elisa Hofmeister ‘18

Takeda Building New Dengue Vaccine Factory in Germany

Takeda, a Japanese pharmaceutical company, is investing one hundred million dollars to build a new Dengue vaccine plant in Singen, Germany. Construction will start now, and the facility should be operational by 2019. The factory is intended for production of their vaccine TAK-003, which is currently in a phase III trial. Dengue virus is the cause of Dengue fever and Dengue hemorrhagic fever, and nearly half of the world's population lives in zones at risk. 

Currently Sanofi's Dengvaxia is the only Dengue virus vaccine on the market, but it is facing many setbacks. There is evidence that Dengue virus can cause antibody-dependent enhancement if a person who has been infected with one of the four serotypes before becomes infected with a different serotype later on. This can cause much more severe disease, and even death. There is debate as to whether Dengvaxia acts as a primary infection, and can cause more severe illness if additional exposure to the virus happens. Takeda's vaccine is designed to avoid this problem, and provide protection against all four serotypes. 

-Anne Sommer

http://www.pmlive.com/pharma_news/takeda_plans_german_plant_to_support_dengue_vaccine_roll-out_1179374
http://www.biopharma-reporter.com/Upstream-Processing/Takeda-building-Dengue-fever-vaccine-plant

A virus that needs multiple virions to infect its host?

An RNA virus that infects mosquitos has been newly discovered. The catch? It separately packages its 5 genomic segments into different virions. Amazingly, the virus tentatively named Guiaco Culex (GCXV), is not the only virus that employs this replication technique. In fact, there are many known plant and fungi viruses, known as multicomponent viruses, that package their segments separately. It is one of the many diverse replication strategies of RNA viruses, and although there is strong evidence that segmentation helps with differential gene expression, it is not well understood why a virus would package its segments separately, since this likely hinders efficient viral transmission.

In order to produce the full infection cycle in multicomponent viruses, all or most segments must be present, although researchers believe that infection by a subset of the segments is enough to induce viral transcription and replication. In the case of GCXV, its likely that 4/5 segments are necessary for infection and transmission, and the fifth segment codes for a nonstructural protein.

GCXV is the first multicomponent animal virus discovered, and it is also the only known enveloped multicomponent virus. It seems to be distantly related to flaviviridae. Hopefully with the discovery of this novel animal virus research into multicomponent viruses will increase, and someday we will understand what is going on with these viruses.

Read the study here:
Ladner, J. T., Wiley, M. R., Bietzel, B., August, A. J., & Dupuis, A. P., II. (2016, September 14). A Multicomponent Animal Virus Isolated from Mosquitoes. Cell Host & Microbe, 20(3), 357-367.

And the NPR article here:


Elisa Hofmeister ‘18