Wednesday, March 5, 2014

Ancient Strains: pithovirus sibericum and smallpox


In February 2012, Scientists from the Institute of Cell Biophysics announced they had regrown plants stored in permafrost by squirrels over 30,000 years ago. The institute raised plants of the silene stenophylla. Writing in the Proceedings of the National Academy of Sciences (PNAS), they note this is the oldest plant material so far to have been brought to life." See: http://www.bbc.com/news/science-environment-17100574
Exciting as this research and discovery was, more concerning perhaps is the recent discovery of pithovirus sibericum, not in an of itself a concern, but with implications for the re-emergence of other more harmful viruses such as ancient smallpox virus, the only human disease ever declared eradicated.

smallpox (variola major)
Recently a French scientific team from the National Center for Scientific Research (CNRS) presented their study on pithovirus sibericum. The Abstract of their study published in the: Proceedings of the National Academy of Sciences, available here:http://www.pnas.org/content/early/2014/02/26/1320670111 states: 

The largest known DNA viruses infect Acanthamoeba and belong to two markedly different families. The Megaviridae exhibit pseudo-icosahedral virions up to 0.7 μm in diameter and adenine–thymine (AT)-rich genomes of up to 1.25 Mb encoding a thousand proteins. Like their Mimivirus prototype discovered 10 y ago, they entirely replicate within cytoplasmic virion factories. In contrast, the recently discovered Pandoraviruses exhibit larger amphora-shaped virions 1 μm in length and guanine–cytosine-rich genomes up to 2.8 Mb long encoding up to 2,500 proteins. Their replication involves the host nucleus. Whereas the Megaviridae share some general features with the previously described icosahedral large DNA viruses, the Pandoraviruses appear unrelated to them. Here we report the discovery of a third type of giant virus combining an even larger pandoravirus-like particle 1.5 μm in length with a surprisingly smaller 600 kb AT-rich genome, a gene content more similar to Iridoviruses and Marseillevirus, and a fully cytoplasmic replication reminiscent of the Megaviridae. This suggests that pandoravirus-like particles may be associated with a variety of virus families more diverse than previously envisioned. This giant virus, named Pithovirus sibericum, was isolated from a >30,000-y-old radiocarbon-dated sample when we initiated a survey of the virome of Siberian permafrost. The revival of such an ancestral amoeba-infecting virus used as a safe indicator of the possible presence of pathogenic DNA viruses, suggests that the thawing of permafrost either from global warming or industrial exploitation of circumpolar regions might not be exempt from future threats to human or animal health.



In multiple reports they have stated that, "The discovery of Pithovirus shows how incomplete our understanding of microscopic biodiversity is when it comes to exploring new environments. And the potentially bad news: the reemergence of other viruses is no longer the domain of science fiction. These include viruses that were long considered eradicated such as smallpox, whose replication process is similar to that of pithovirus. This is an indication that viruses pathogenic for human or animals might also be preserved in old permafrost layers, including some that have caused planet wide epidemics in the past, said Jean Michel Claverie, one of the study's co-authors." Prof. Claverie warns that exposing deep layers could expose new viral threats. He has been quoted as saying that 'ancient strains of the smallpox virus, which was declared eradicated 30 years ago, could pose a risk. "If it is true that these viruses survive in the same way those amoeba viruses survive, then smallpox is not eradicated from the planet--only the surface." "By going deeper we may reactive the possibility that smallpox could become a disease of humans in modern times." See: http://www.bbc.com/news/science-environment-26387276

In a February, 2014 report entitled: Poxvirus Viability and Signatures in Historical Relics, published in Emerging Infectious Diseases (see:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901489/), the authors Andrea M. McCollum, Yu Li and CDC orthopox expert Inger K. Damon, suggest that "Although it has been >30 years since the eradication of smallpox, the unearthing of well preserved tissue material in which the virus may reside has called into question the viability of variola virus decades or centuries after its original occurrence. Experimental data to address the long-term stability and viability of the virus are limited. There are several instances of well preserved corpses and tissue that have been examined for poxvirus viability and viral DNA. These historical specimens cause concern for potential exposures, and each situation should be approached cautiously and independently with the available information. Nevertheless, these specimens provide information on the history of a major disease and vaccination against it. 

www.vaccines.mil
Both Prof. Claverie and the authors of the EID study, one of whom I had the pleasure of meeting at a major smallpox bio-security conference in Geneve, bring up valid points with regard to the potential risk of re-emergence and exposure to the only successfully eradicated human disease. But eradication may now be as Prof. Claverie states "not eradication from the planet --only the surface." Maintaining our Strategic National Stockpiles and continuing research on smallpox remains a vital aspect of bio-defence and US national security. For further reading I recommend: Orthopox Targets for the Development of New Anti-viral Agents published by NIH (See: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773844/)
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