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/µL. 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.
Thursday, May 28, 2015
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
MERS on the Move
This week, MERS has popped up in Bahrain, Quatar, Saudi
Arabia, and … Korea?
Korean patient zero is thought to be a 68-year old male who
traveled to Bahrain on a business trip between April 18th and May 3rd.
He visited a hospital before it was known that he was infected, and he infected
a 76-year old man. As a result, the hospital quarantined 64 workers. The public
health authorities of nearby countries, including Taiwan and Thailand, are on high
alert for the virus, although they have not found any cases yet.
True to its name, MERS (Middle
Eastern Respiratory Syndrome) primarily resides in the Middle East, but back in
2012, it has a massive outbreak that killed about 400 people in Europe, the
Middle East, and in East Asia (it spread to North America but nobody there
died). (http://www.who.int/csr/disease/coronavirus_infections/MERSCov_WHO_KSA_Mission_Jun13_.pdf).
The first recorded case in this current outbreak occurred in a 29-year old man in
Qatar who transported camels in his truck for a living (which makes sense since
camels are a known reservoir of MERS). The camels he was transporting at the
time he was diagnosed all tested positive for MERS-CoV. Most of the other cases
in Saudi Arabia have been in middle-aged or older individuals. Currently, 9
individuals are receiving treatment for MERS, and another is in home quarantine.
The true origin of this outbreak
may have been as early as February, when 3 middle-aged men and one middle-aged woman
were infected, and the WHO called the country out for not doing a better job of
containing the virus. While these numbers don’t seem like much of an outbreak,
MERS has a mortality rate of about 27% (http://www.who.int/csr/disease/coronavirus_infections/faq/en/).
--Joe
Wednesday, May 20, 2015
Norovirus outbreak on ship departing from San Francisco
An outbreak of norovirus occurred last week on a Princess Cruise ship departing from nearby San Francisco en route to Hawaii. Of the 3,681 people on board, over 150 passengers and crewmembers were infected with the virus aboard the Star Princess. Norovirus was detected in preliminary tests collected onboard the ship, and stool samples have been collected and sent to the CDC for further testing.
After detection, sanitation procedures were ramped up to prevent further transmission of the virus. Passengers were also advised of ways to minimize transmission and their risk of infection, including washing their hands thoroughly, and using only restrooms in their cabin. Furthermore, passengers were not allowed to disembark the ship, due to the possible risk of transmission. Upon its return to San Francisco, the ship was thoroughly cleansed in preparation for its next cruise.
This latest outbreak has further affirmed the reputation of cruise ships as a breeding ground for extremely contagious pathogens such as Norovirus. In fact, this incident represents the sixth time in 2015 that a cruise ship has reported a Norovirus outbreak en route to a US port. The Princess Cruise line is no stranger to Norovirus outbreaks; in 2014 alone, outbreaks operated by Princess Cruises accounted for seven of the sixteen documented outbreaks on cruise ships in 2012.
http://sfbay.ca/2015/05/15/virus-sickens-150-on-star-princess-cruise-ship/
--Andrew Duong
After detection, sanitation procedures were ramped up to prevent further transmission of the virus. Passengers were also advised of ways to minimize transmission and their risk of infection, including washing their hands thoroughly, and using only restrooms in their cabin. Furthermore, passengers were not allowed to disembark the ship, due to the possible risk of transmission. Upon its return to San Francisco, the ship was thoroughly cleansed in preparation for its next cruise.
This latest outbreak has further affirmed the reputation of cruise ships as a breeding ground for extremely contagious pathogens such as Norovirus. In fact, this incident represents the sixth time in 2015 that a cruise ship has reported a Norovirus outbreak en route to a US port. The Princess Cruise line is no stranger to Norovirus outbreaks; in 2014 alone, outbreaks operated by Princess Cruises accounted for seven of the sixteen documented outbreaks on cruise ships in 2012.
http://sfbay.ca/2015/05/15/virus-sickens-150-on-star-princess-cruise-ship/
--Andrew Duong
Wednesday, May 13, 2015
Rabies in Brain Imaging
We spent a bit of time talking about rabies in Humans and Viruses. A scary zoonotic infection that kills if untreated, rabies has been a scourge of humanity since ancient times. Over the past few years however, Ed Callaway of the Salk institute has been working with a deletion mutant strain of rabies with a GFP gene added. Rabies infects neurons through axon terminals and spreads backward (i.e. in a retrograde direction). This mutant strain replicates within host cells, but cannot spread beyond the first neuron they infect. Thus, the vector is not only safe, but it also doesn’t lead to any background fluorescence other than that which comes from the cells it infects.
http://www.newyorker.com/tech/elements/the-brighter-side-of-rabies
http://www.nature.com/nmeth/journal/v4/n1/full/nmeth999.html
--Joe
Monday, May 11, 2015
Rift Valley Fever Virus Helps Understand Viral Replication
A group in Montreal, Canada is attempting to understand hemorrgaic fever viruses through the lens of basic research. By understanding the mechinism by which the viruses replicate adn mutate, they hope to create possible drug targets for future therapeutics which may be a more economically viable solution to such diease than a vaccine (vaccines have been difficult to finance becasue many of these viruses occur in poor countries where there is not a large enough financial incentive for large scale produciton).
Using Rift Valley Fever Virus, researches attempted to characterize the method of replication of the virus. Using nuclear magnetic imaging (NMR), the researches attempting to characterize what each of the viral proteins were responsible for replication. They discovered that a non-structural protein (NSs) of the virus binds to Transcription Factor II in the cell and creates nuclear filaments. The viral protein that does this looks similar to the human DNA repair proteins (sharing similar structural motifs) and may be a potential candidate for drug-targeting, since inhibiting the protein's action reduces virulence.
Paper:http://www.pnas.org/content/early/2015/04/22/1503688112
---Lauren
Using Rift Valley Fever Virus, researches attempted to characterize the method of replication of the virus. Using nuclear magnetic imaging (NMR), the researches attempting to characterize what each of the viral proteins were responsible for replication. They discovered that a non-structural protein (NSs) of the virus binds to Transcription Factor II in the cell and creates nuclear filaments. The viral protein that does this looks similar to the human DNA repair proteins (sharing similar structural motifs) and may be a potential candidate for drug-targeting, since inhibiting the protein's action reduces virulence.
Paper:http://www.pnas.org/content/early/2015/04/22/1503688112
---Lauren
Mutagenesis Induction in Viruses
Viruses - particularly retroviruses like HIV - are notorious for their ability to mutate. The rapid replication of viruses paired with their high mutation rate allow viruses to adapt to their host quickly. However, mutations are only beneficial to a certain extent, and most mutations are likely maladaptive. Using this information, scientists at the University of Chicago and MIT have been able to induce mutagenesis in viruses, increasing their rate of mutation to a point where the virus can no longer function effectively. Moreover, these scientists have developed a spectroscopy method that further elucidates the mechanism behind nucleotide analogs.
The researchers used an anti-HIV agent called KP1212 that evades viral detection and infiltrates a viruses genome. KP1212 functions essentially as a nucleotide analog that mimic DNA bases and result in mismatching of the normal adenosine-thymine, and cytosine-guanine base pairings in DNA. KP1212 is believed to work by repositioning hydrogen atoms in DNA, and resulting in faulty hydrogen bonding.
The use of two-dimensional infrared microscopy by the scientists to examine the structure of mutated viral DNA is novel, as scientists typically use nuclear magnetic resonance. The benefit of infrared microscopy is that scientists can examine the quickly changing structures of mutagenic viral DNA in aqueous solution (the natural environment of cells) as opposed to organic solvents. The ability of infrared microscopy to detect different mutagenic viral DNA structures, which quickly change shape and are keenly sensitive to time-changes, has resulted in the discovery of many different tautomers invoked by the KP1212 molecule.
Source: http://news.uchicago.edu/article/2015/04/14/shape-shifting-molecule-tricks-viruses-mutating-themselves-death
--Andrew Duong
The researchers used an anti-HIV agent called KP1212 that evades viral detection and infiltrates a viruses genome. KP1212 functions essentially as a nucleotide analog that mimic DNA bases and result in mismatching of the normal adenosine-thymine, and cytosine-guanine base pairings in DNA. KP1212 is believed to work by repositioning hydrogen atoms in DNA, and resulting in faulty hydrogen bonding.
The use of two-dimensional infrared microscopy by the scientists to examine the structure of mutated viral DNA is novel, as scientists typically use nuclear magnetic resonance. The benefit of infrared microscopy is that scientists can examine the quickly changing structures of mutagenic viral DNA in aqueous solution (the natural environment of cells) as opposed to organic solvents. The ability of infrared microscopy to detect different mutagenic viral DNA structures, which quickly change shape and are keenly sensitive to time-changes, has resulted in the discovery of many different tautomers invoked by the KP1212 molecule.
Source: http://news.uchicago.edu/article/2015/04/14/shape-shifting-molecule-tricks-viruses-mutating-themselves-death
--Andrew Duong
Ebola found in the eye of "cured" patient
Following up on last week's post about the alleged sexual transmission of Ebola through a previously infected man's sperm, a new report this week has found a new potential reservoir for Ebola: the inside of a person's eye. The eye is a prime place for a virus to reside because the inside of the eye (alongside the testicles) exhibit immune privilege, a phenomenon wherein certain immune molecules and compounds are found at lower concentrations in these areas. Ebola was found in the eye of Dr. Ian Crozier, an American doctor who was infected with Ebola, and "recovered" from the virus in October. However, months later, high pressure in his eye developed, resulting in blurred vision and discomfort for Dr. Crozier. Knowing that Dr. Crozier was once infected with Ebola just a few months ago, opthalmologists at Emory University drew fluid from the inside of his eye to test if Ebola was responsible for the pressure build-up inside his eye.
Surprisingly, laboratory tests revealed the presence of Ebola in the inside of the Dr. Crozier's eyes, but not in his tears or surface film, meaning that while Ebola persisted in his system, his potential to infect others was very low. With no approved treatments for Ebola, Dr. Crozier's condition deteriorated rapidly. In a particularly gruesome incident, Dr. Crozier's eye changed color from blue to green for several weeks. Eye color change is extremely rare for viral infections, and usually indicate a severe infection. Scientists are preliminarily dubbing the new eye condition post-Ebola syndrome, as reports from West Africa suggest that other recovered patients have experienced similar eye problems.
Luckily for Dr. Crozier, an experimental treatment consisting of steroids and an antiviral has resulted in his gradual recovery, showing promise for treatments currently in development against the virus. His eye color, for example, reverted back to its natural blue color, and parts of his vision are returning. However, it is still too early to tell what the long-term effects of Ebola are, and if Dr. Crozier will ever fully recover from the disease. Future research is critically needed to study the chronic effects of Ebola, especially given that there have been relatively few infections and even fewer survivors prior to the 2014 West African Ebola outbreak.
Source: http://www.nytimes.com/2015/05/08/health/weeks-after-his-recovery-ebola-lurked-in-a-doctors-eye.html
--Andrew Duong
Surprisingly, laboratory tests revealed the presence of Ebola in the inside of the Dr. Crozier's eyes, but not in his tears or surface film, meaning that while Ebola persisted in his system, his potential to infect others was very low. With no approved treatments for Ebola, Dr. Crozier's condition deteriorated rapidly. In a particularly gruesome incident, Dr. Crozier's eye changed color from blue to green for several weeks. Eye color change is extremely rare for viral infections, and usually indicate a severe infection. Scientists are preliminarily dubbing the new eye condition post-Ebola syndrome, as reports from West Africa suggest that other recovered patients have experienced similar eye problems.
Luckily for Dr. Crozier, an experimental treatment consisting of steroids and an antiviral has resulted in his gradual recovery, showing promise for treatments currently in development against the virus. His eye color, for example, reverted back to its natural blue color, and parts of his vision are returning. However, it is still too early to tell what the long-term effects of Ebola are, and if Dr. Crozier will ever fully recover from the disease. Future research is critically needed to study the chronic effects of Ebola, especially given that there have been relatively few infections and even fewer survivors prior to the 2014 West African Ebola outbreak.
Source: http://www.nytimes.com/2015/05/08/health/weeks-after-his-recovery-ebola-lurked-in-a-doctors-eye.html
--Andrew Duong
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