Friday, October 31, 2014

Smallpox: A New Kind of Computer Virus?

Source: Jan Bajtlik, New York Times

In 1975, smallpox was eradicated. Our war against one of humankind's greatest killers, with an estimated death toll of one billion people, was over. Humanity had won. There have been no cases of naturally occurring smallpox in almost four decades. 

And yet, as a New York Times op-ed argues, smallpox is just a mouse-click away. What could stop someone from searching up the genome and sending it out for synthesis? Scientists have it even easier; with the right machines, they could synthesize it from the comfort of their lab. Could inserting this synthetic genome into a human cell produce infectious virions?

Leonard Adleman, the op-ed author, says yes. He cites a 2002 study done by Cello, Paul and Wimmer at State University of New York at Stony Brook. In it, they succeeded in synthesizing a poliovirus genome from scratch and showing its moderate infectivity in mice. 

However, this is poor evidence that infectious smallpox could also be created in this way. First of all, poliovirus has a small RNA genome that is about 7,500 base pairs long. Smallpox has one of the largest DNA genomes, clocking in at around 200,000 base pairs. That alone is telling. Especially given the limitations of chemical DNA/RNA synthesis. Even for the small poliovirus genome, only small portions of it could be synthesized at a time. All of these short fragments would then have to be connected in the correct order. With a 200,000 bp long genome, that task would be herculean. 

Additionally, the smallpox DNA cannot infect cells all by its lonesome. It is a huge virus that carries with it many of the proteins it needs for replication and other functions. Without those, it cannot effectively propagate. Could the proteins be translated from the genome or also chemically synthesized? Perhaps. But that would be another major obstacle to overcome before creating a fully infectious smallpox virus. 

These two considerations alone severely undermine the validity of this op-ed's dire warning. Although there may be potential for bioterrorism from an adequately equipped lab and open-source infectious disease databases, especially with other viruses, the resurrection of smallpox is not on the horizon. 

  3. Knipe, D. M. & Howley, P. M. (Eds.). (2013). Fields Virology (6th ed.). Philadelphia, PA: Lipincott Williams & Wilkins. Accessed via OvidSP through Stanford.
Tina Ju

Thursday, October 30, 2014

Densovirus as a Beneficial Virus

     So this isn't a human virus, but I think it's cool enough to be relevant. A new study released claims that Densovirus is a mutual symbiont of a moth (Helicoverpa armigera) and protects against baculovirus. This breaks a central dogma of viruses that states all viruses are detrimental to health. This study shows that Densovirus infection is beneficial to this moth. Helicoverpa armigera Densovirus-1 (HaDNV-1) is wide-spread in adult populations of these moths (>67%).  The study found a strong negative interaction between HaDNV-1 and nucleopolyhedrovirus. Bioassays also showed that moths infected with HaDNV-1 had increased resistance to nucleopolyhderovirus. The researchers found no negative effect on the moths from HaDNV-1 infection. Another interesting thing is the fact that the virus could be transferred horizontally and vertically.

    When I first read this, I thought it was pretty cool because it shows a virus being beneficial to their hosts. However, the moth is actually a global crop pest and nucleopolyhedrovirus is used in biopesticides against the moth. soo..... We need to make sure these moths don't get infected with densovirus.


- Jimmy

Combatting Viruses with Bacteria

Dengue fever has rampantly spread throughout the glove, with now more than 2.5 billion people at risk and an estimated over 400 million infected. Dengue is spread by the A. Aegypti mosquito; due to climate change and an increase in urbanization, these mosquitos now have an increased range in infection and a greater density of possible hosts. With no known vaccine or cure for dengue virus, the most prudent form of disease control is to control vectors - the mosquitos. While insecticides are an attractive option, they can pose serious risk to via biomagnification and toxicity. Recently, Monash University in Australia has attempted to curb the growing Aegypti mosquito population by intentionally infecting these mosquitos with a bacteria known as Wolbachia. In lab, Wolbachia has been known to dramatically decrease the rate of viral replication of dengue; additionally, Wolbachia can be spread at the cellular level to young. Several populations of infected mosquitos have been released to yards and pools around Australia in an attempt to cause a bacterial epidemic in the Aegyptis population.

Alex Lindqwister

Stanford ER Surgeon being monitored for Ebola "out of an abundance of caution"

     A Stanford ER surgeon, Dr. Colin Bucks, is being monitored for Ebola "out of an abundance of caution." Dr. Colin Bucks is the medical director of disaster preparedness for Stanford Health Care and is a clinical assistant professor of surgery at Stanford medical school's department of emergency medicine. Dr. Bucks was volunteering in Liberia with International Medical Corps, a LA-based nonprofit that's not affiliated with Stanford in any way.
    Stanford Health Care announced last Thursday that Bucks would be isolated for 21 days "out of an abundance of caution" following his last known contact with an Ebola-infected patient. 21 days is the incubation period for Ebola. He has been healthy and asymptomatic since coming back. This response is interesting as we have learned that an Ebola-infected individual is only contagious when he/she is also symptomatic. It seems like an over-reaction and even Stanford Health Care admits that it's kind of a severe reaction. However, we do need to be careful just in case he's infected with a mutated strain that makes him contagious even when he's asymptomatic. This decision was made by Stanford Healthcare according to its emerging infectious disease response plan, which are based off CDC's guidelines.
   Dr. Bucks is on paid leave and is "very cooperative." County health officials take his temperature twice a day.
   I initially thought this was an overreaction, but it's actually a pretty chill quarantine. It sounds like a lot of resources are going into this. Speaking of lots of resources, all major hospitals are undergoing significant "Ebola training" for relevant employees. It's not the most cost effective approach and it'd be great if all that training money was put into Africa instead.

virologically yours


The King of Terrors

        I am reading “The Mississippi Valley’s Great Yellow Fever Epidemic of 1878” by Khaled J. Bloom, and as you can imagine I have yellow fever on the brain.  The confusion that initially surrounded Yellow Jack—the name for yellow fever at the time—was deeply entrenched in the medical community.  Some health officials believed that filth and dirty water were the causes of yellow fever.  Others believed that there was something inherent in the atmosphere of cities that bred disease.  And others believed that it had something to do with moist, warm air.  All these theories were close to some type of truth, but they were muddled with panic and confusion.  It makes sense that the people of Southern United States couldn’t wrap their minds around this disease because the virus nearly decimated certain states.  In 1853 in New Orleans, Louisiana there were 40,000 cases with 11,000 deaths.  Memphis was hit so bad that when the disease returned in 1879, the federal government was considering destroying the entire city of Memphis.  The disease quickly became known as the King of Terrors.  Although the scientific community didn’t know much about yellow fever it did loosely understand that yellow fever was a disease intertwined not only with people but also with the environment.   
            Mosquito vector-borne diseases are tough for several reasons.  Firstly, the life cycles of mosquitos are complicated and include several stages with their own identities and properties.  Secondly, the ecology and preferred environment of mosquitos play a big part in mosquito-vector diseases.  Lastly, these guys can fly. Recently diseases such as yellow fever, dengue, and malaria have come up in the discussion of climate change (global warming!).  As temperatures increases and climates shift, the range of habitat for insect vectors also shifts.  Although there is merit to this idea, it seems to me like the histories of mosquito vector diseases have more to do with human activities and their effect on ecology than climate change do.  Several articles also suggest human factors as a major driving point for the spread of the mosquito.  Clearing forests, development into mosquito habitat, and everyday behavior play a large role in modifying the range of a mosquito. 
       When I mention the developed world, the specific area that I envision is Palo Alto, California.  And surprise surprise the yellow fever mosquito has almost made its way here to Palo Alto, the land of bike lanes and bistros.  In 2014 the San Mateo County Mosquito and Vector Control District found Aedes aegypti mosquitos at thirteen locations.  The first location was in Menlo Park at the Holy Cross Cemetery.  Furthermore this was the third mosquito in the Aedes genus that was found in Los Angeles, which isn’t too far away from Palo Alto.  Although there was no disease associated with these mosquitos, I think the Ebola epidemic suggests how easy viruses can move in this day and age. Unlike Ebola where an infected individual would have to cross an ocean to reach the US, an individual infected with yellow fever would have to travel up from any country in Southern America to reach the US.  No matter how improbable it seems like this would happen, it is possible, and that is what matters.

-Nalani Wakinekona


Wednesday, October 29, 2014

No More Funding for Mutant Virus Development

The Obama administration recently announced that it will no longer fund research that focuses on creating "super-viruses," viruses that are evolved to be more deadly and more dangerous than the natural ones. This has significant implications for researchers in this field because the government is one of the main providers of funding for biomedical research. The government is justifying its action by claiming that developing and researching super viruses poses a threat to society. Opponents of the government's decision claim that researching the ways in which viruses can evolve is crucial in understanding them. Furthermore, inducing the mutations in certain virus before they occur in nature will be important in developing treatments. The government has stopped funding research and has recommended that sponsors, who provide the other sources of research, stop funding as well. It's waiting on the National Science Advisory Board for Biosecurity and the National Research Council to review the risks and benefits of this type of research to solidify a policy.



Viroids: a look at the smallest of the small and the origins of life

(shamefully stolen, but can’t find the original source.)

Last week in class we discussed 4 possible sources for viruses:
     1.  Viruses were present in primordial soup
           2. Viruses emanate from space (Fred Hoyle)
       3. Viruses assimilated from parts of other cells
       4.     Viruses are degenerate cells

The review“Viroids: Survivors from the RNA world?” from Annual Review of Microbiology, elaborates on the first possibility of sources for (plant) viruses and the rest of life. The article looks at the evidence from viroids and their close relatives to better understand their origins and the origins of life.  In addition to viroids, the review also discusses plant viroid-like satellite RNAs, retroviroids, and hepatitis delta virus (HDV), which have the smallest genome of animal viruses.

 According to this article, the consensus is that RNA emerged before DNA and proteins. DNA and proteins eventually took over life on earth, and relegated RNA to intermediate functions.  But are there survivors from this first RNA world?  

(more shameful stealing,
Primordial Soup – better known as the RNA World? 

Theories and thoughts on origins of viroids: 
       1.     Viroids are escaped introns. However, viroids do not seem to be simplified version of viruses or transposons because of their distinct reaction mechanisms. Additionally, viroids, such as PSTVd, weren’t found in the cellular DNA of normal plants.
       2.     Viroids are surviving relics of a precelllar evolution in an RNA World.

Most of the article’s evidence affirming viroids as the survivors of precellular ancestors relies on demonstrating that they could fit in an RNA world. 

Evidence for viroids as relics of an RNA World:
·        Viroids have small genomes and are nonprotein-coding RNAs.
  The underlying idea is the simplest is the oldest.
·        High G+C content and circularity
  The underlying idea is that this increases replication fidelity helps the genome replicate   completely, meaning greater stability.  The RNA world is possible!
·          A number of viroids have structural periodicity.
   The underlying idea is that in addition to being associated with protein binding, structural      periodicity may have allowed larger genomes to evolve. Modular evolution would have allowed for    high mutation rates, which would have shortened the evolutionary time required to make a complex    structure, and possibly allow for complex structures that may have not been directly selected.    Complex life could have come from an RNA world!
·         Some viroids have hammerhead ribozymes, the “finger print of the RNA world.”
   The underlying idea is that the small size and relatively low complexity of hammerhead ribozymes    make viroid replication in a pre-protein world possible.


Is such a thing what actually happened? The jury is still out.

Pithy quotes from the review:
“Thus viroids are essentially transcriptional parasites, whereas viruses are essentially translational parasites. “

By Olivia