Saturday, June 6, 2015

Contagiousness of MERS

The recent outbreak of MERS - Middle East respiratory syndrome virus - has infected at least 36 people in South Korea.  As a result, the outbreak has been a source of concern for epidemiologists around the world.  Efforts to quarantine people and camels have followed in an attempt to squash the outbreak.

Perhaps surprisingly, however, the MERS virus is not highly contagious; previous studies have found that its R0 is 2-3, meaning that the average infected person only infects two to three other people.  In fact, MERS is thought to be spread primarily zoonotically (from camels to humans).

It is important to note that while the MERS virus is not highly contagious, it is still important to monitor the outbreak and prevent it from growing any larger.  One issue commonly found in reports on the contagiousness of viruses is that there is an implication that less contagious viruses cannot manifest into epidemics and that they are less serious than highly contagious viruses.  However, with HIV - a virus that is relatively low in contagion (e.g. exposure to the virus via an infected needlestick seldom leads to infection) - we see that it can still lead to a deadly epidemic.  More recently, Ebola, a virus with an R0 if 1.5-2.5 manifested itself into the huge Ebola outbreak in West Africa.

Thus, articles reporting on the contagiousness of viruses should be taken just as a presentation of the facts, or as one of many indicators of the epidemic potential of a virus.

Source: http://abcnews.go.com/Health/infectious-mers-virus-compared-viruses/story?id=31535945

--Andrew Duong

Thursday, June 4, 2015

Inexpensive Blood Test Reveals Your Viral Exposure History?

A international team of scientists has just developed a comprehensive screening mechanism called VirScan. This technology is a high-throughput method that comprehensively analyzes antiviral antibodies using immunoprecipittion and parallel DNA sequencing of a bacteriophage library that displays proteome-wide peptides from all known human viruses. While it might not be a complete history, VirScan revealed the presence of antibodies to 10 or more different viral species per person in a 569-person study that included subjects from the United States, Peru, Thailand, and South Africa. At least two of the individuals tested had at least antibodies against 84 different viral species. The study found 206 different viral species in total, and over 1000 strains.
            Widespread adoption of VirScan could be a great diagnostic and research tool. Current serological testing is usually focused on testing for one pathogen at a time. The analysis costs about $25 per person and only 1 microliter of blood. One of the unexpected results of VirScan was that different people produced structurally similar antibodies to a small number of “public” epitopes for many different viral species. The team hopes that VirScan can be used to study the effect of host-virome interactions on human health, and possibly be expanded for test for bacterial, fungal, and protozoan pathogens.
            Clinically, VirScan could be used to identify antibodies for a virus that a patient might not be aware he/she was exposed to, especially latent viruses that can lead to cancer (e.g. hepatitis C). VirScan could also be used to draw associations between viruses and chronic conditions such as diabetes and chronic fatigue syndrome.



 The color of each cell in the grid depicts the relative number of antigenic epitopes detected for a virus (rows) in each sample (column).


Other Sources:



--Joe

Wednesday, June 3, 2015

A New Way to Look at Viruses—Weighing by Mass Spectrometry

            There are various techniques that have been used over the years to study viruses. Scientists have studied their pathological effects in living systems, their cytopathic effects in cell culture. We can directly observe viruses through x-ray crystallography.

Pathological Approach:
 Varicella-zoster virus is one of a myriad of viruses that causes distinctive signs and symptoms/pathologies. The body’s immune response to the varicella-zoster virus causes the characteristic red spots of chickenpox. The list goes on. Macroscopic diagnoses can be used in epidemiological studies and for diagnostic purposes. Before the development of modern laboratory and imaging techniques, this was how many viral illnesses were first characterized.

Cytopathic Effect:
Characteristic deformities that certain viruses cause to the cells they infect. For example, some herpes viruses cause multinucleation. Respiratory syncytia virus (Paramyxoviridae) causes syncytia (fusion of multiple cells into one large one).

--multinucleation (wikimedia commons)



X-Ray Crystallography:
Was used to produce the first pictures of DNA--it involves studying the diffractions of x-rays from crystalline atoms.

--X-ray crystallography of Poliovirus type 1


Scanning Electron Microscopy:

Scanning electron microscopes produce 3-dimensional images. They can show topographical details of a virus.


HSV-1 SEM, http://coldsoreshomeremedies.ca/index.php/2009/02/what-is-a-cold-sore/


Transmission Electron Microscopy:

TEM has a higher magnification and greater resolution, but produces 2-dimensional rather than 3-dimensional images.




However, there has just been a study to use a different imaging technique to study viruses: mass spectrometry. For the first time ever, we can weigh an intact virus. Specifically, the study used heavy-ion mass spectrometry MS to study a mixture of intact virus particles. The team, led by Carnegie Mellon University’s Mark Bier and his graduate student Logan Plath, used samples containing two varieties of a cowpea (black-eyed pea) mosaic virus (a plant virus); they found that one virus weighted 5.65 megadaltons, and the other 4.84 megadaltons. Both of these numbers were approximately that of the theorized masses of the viruses.
Previously, mass spectrometry’s use in virology has been limited because intact viruses have been too large. To get around this problem, Bier’s group used a cryodetector-based matrix-assisted laser desorption/ionization time of flight mass spectrometer (that’s a real mouthful), called a Macromizer. The 3.75 meter-long apparatus can analyze low charge heavy ions with greater sensitivity than standard mass spectrometers.


--black-eyed pea mosaic virus--what's it gonna do with all those megadaltons inside that trunk?
https://www.behance.net/gallery/4030849/Cowpea-Mosaic-Virus

http://phys.org/news/2015-06-chemists-intact-virus-mixture-mass.html 
http://www.sciencedirect.com/science/article/pii/S0166093414004443


--Joe


Thursday, May 28, 2015

Time Thogoto Oklahoma, They've Got the Bourbon

Orthomyxoviridae, the familial host of our familiar friend influenza, is making some new headlines after a relatively unimpressive flu season this past winter. It seems as if the midwest will be plagued by the negative stranded, RNA, multipartite genome family of Orthomyxoviridae into the summer, as the relatively new Bourbon virus has been discovered in Oklahoma.

Bourbon virus, a newly categorized member of the genus Thogotovirus, has just been identified in Payne county, Oklahoma. Transmitted by ticks, state health officials are now advising residents of Payne county and the state of Oklahoma to be extra cautious while being active outdoors, making sure to use DEET, other insect repellants, long sleeves, and pants. State epidemiologists also warn that the recent wet weather heading into the summer may cause favorable conditions for an above average tick population.

The new patient is the second identified case of Bourbon virus infection ever. Although the patient recovered from the disease in May of 2014, the public health officials released information to the public that the patient did have the rare viral disease and contracted it within Payne county.

The first person to be identified with Bourbon virus was a resident of Kentucky who came down with a serious viral infection within a week of having received a tick bite. According to the Emerging Infectious Disease report as published by the CDC, the patient was a male older than the age of 50 who had been doing yard work on his property when he realized that he had received several tick bites. The patient removed a large engorged tick from his shoulder just two days before he came down with malaise, nausea, and diarrhea. A day after the original presentation of symptoms, the patient further developed fever, myalgia, chills, anorexia, and arthralgia.

Upon admission to the hospital, the patient experienced diminished consciousness, was running a slight fever of 99.9 degrees fahrenheit, and had an increased blood pressure of 151/65 mmHg. Interestingly, the patient also presented with a papular rash on his trunk. I am not aware of any other Orthomyxovirus that presents initially with a rash before the onset of further symptoms. One other virus that presents early on with a papular rash is Measles Virus, a member of the family Paramyxoviridae. It is believed that many viral rashes, like the typical rash in Measles, presents due to a cell mediated attack on virus that is located within skin cells and the vasculature near the dermis (Klimpel, 1996). This may indicate that the patient mounts an immune response to the Bourban Virus infection early on, but without early supportive treatment, may not be able to keep up with viral replication, and the immune system succumbs to viremia.

The patient then began to develop thrombocytopenia with a platelet count of 72,000 cells/┬ÁL. Thrombocytopenia is seen in many viral infections that also include exanthems, such as Varicella Zoster, Rubella, Mumps, and Parvovirus. Kosoy et al. of the CDC remark that this observed reduction in the patient's platelets coupled with leukopenia is likely secondary to acute bone marrow suppression.

Ultimately, the patient was treated for what the physicians thought was a bacterial infection acquired through tick bite. He was given Doxycycline intravenously 100 mg/hour, followed by a broad spectrum antimicrobial treatment on day 10 of illness. Unfortunately, the patient succumbed to the virus due to progressive heart failure that eventually lead to sustained ventricular tachycardia with persistent hypotension and eventual pulseless electrical activity.

The authors of the Emerging Infectious Disease paper suggest that severe viral febrile illnesses coupled with thrombocytopenia are likely underestimated, as Heartland Virus, and other tick transmitted viral diseases continue to pop up. Hopefully physicians in the midwest are able to recognize these viral symptoms early on so that good supportive treatment can help avoid mortality.

- Marcus Munoz


References:

Klimpel GR. Immune Defenses. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 50. Available from: http://www.ncbi.nlm.nih.gov/books/NBK8423/

Kosoy, Olga I., et al. "Novel Thogotovirus Associated with Febrile Illness and Death, United States, 2014."Emerging infectious diseases 21.5 (2015): 760.

Herpes used in Anti Skin Cancer Therapy

http://www.welt.de/gesundheit/article135950203/Ist-Krebs-die-beste-Art-zu-sterben.html






            Most of the herpesviruses we’ve talked about cause apparent skin pathologies. But in a recent study, Virotherapy, the selective use of genetically engineered viruses to treat disease, successfully treated aggressive melanoma. The virus that the study employed was a modified version of herpes simplex virus type 1. The therapeutic strain, named T-VEC, was developed back in 2006 through the deletion of 2 nonessential viral genes. The first is herpes virus neurovirulence factor gene (ICP34.5); this deletion attenuates the virus, and causes it to infect tumor cells more easily. The second is ICP47, a gene that suppresses host cell antigen presentation (i.e. so the patient’s immune system can better target the cancer cells). T-VEC also has a human gene called granulocyte macrophage colony-stimulating factor. In other words, this gene’s product recruits and stimulates macrophages, which are antigen-presenting cells.
            The study injected the mutant into stage III and IV melanoma patients as part of a stage 3 clinical trial. The average survival time of the patients who received the virotherapy was 41 months, as compared to 21.5 months for the control group. These findings could be key in the development of an effective anti-melanoma therapy. In 2011, 65,647 people were diagnosed with melanoma in the United States, of which 9,128 died (13% case fatality!). Melanoma deaths cause about $3.5 billion of lost productivity in the United States alone every year. These results are exciting, but of course, an actual drug may still be a ways off. However, virotherapy is expandable to other types of cancers too, so it could be a useful addition to the current arsenal of cancer therapies.








--Joe


Saturday, May 23, 2015

Sailing the Seven Viro-seas


--A photo that the French Consulate took of the Tara, a research vessel dedicated to studying the diversity of oceanic plankton and their viruses, from (http://www.sciencetimes.com/articles/6613/20150523/sampling-the-world-s-oceans-on-a-global-scale-reveals-the-complex-relationship-between-viruses-and-microbes.htm)

            In March 2011, the Tara, a 36-meter research ship, started a series of expeditions that would form part of a multi-year journey-- about 180,000 miles of sailing. One of the scientists on board, Melissa Duhaime, spent most of the voyage not looking at open ocean animals, but at the diversity of oceanic plankton and… and viruses?  
Duhaime and her colleagues set out on a quest to quantify the diversity of viruses in the oceans. Through thousands of genetic screens of microorganisms in seawater, over 35,000 species of plankton. most of which were previously undescribed. Oceanic viruses have only been studied since the 1980’s, but no study has even been this ambitious. This study was truly vast in its scope, as it sampled the microbiota between the surface and 6,561 feet deep. The study (http://www.sciencemag.org/content/348/6237/1261498) used quantitative double-stranded DNA and protein analysis to screen for pelagic DNA and RNA viruses. The team found 5,476 species of viruses; only 39 of these were previously known to science. Because of plankton’s importance in global carbon cycles (and therefore importance to the regulation of Earth’s climate), understanding the pathogens of plankton is an important part of understanding marine ecosystems.
            They also found that viral communities varied based on the physical conditions and organisms that lived in a given region. They concluded that viruses are passively transported on oceanic currents and locally structured by environmental conditions that affect host community structure. Their findings suggested that a “seed-bank” hypothesis (i.e. high local genetic diversity can exist when individual communities diverge from a common and relatively limited global “common” gene pool) could be used to describe the variations in viral communities across the world’s oceans. 

The ocean is a huge place, though. There are undoubtedly even more discoveries to be made about the virology of the oceans. 




More references:

http://www.sciencetimes.com/articles/6613/20150523/sampling-the-world-s-oceans-on-a-global-scale-reveals-the-complex-relationship-between-viruses-and-microbes.htm 


--Joe