Saturday, October 06, 2007

ORIGIN OF SMALLPOX


Fig. 3. (taken from PNAS). Hypotheses of the origin of VARV. Event 0, The high similarity of VARV to CMLV and TATV genome sequences suggests that TATV and CMLV share a more recent common ancestor with VARV than do other known Orthopoxvirus species. Event 1, hypothesis A: An ancestral VARV diverged into two primary clades (P-I and P-II) and evolved independently in the Old World and the New World by following its human hosts. Event 1, hypothesis B: The divergence of P-I/P-II in Africa. Event 2, hypotheses A and B: The long single branch and subsequent radiation of P-I suggest that the ancestral VARV of P-I probably originated in Northeast Asia and that the smallpox endemics of P-I started to spread to East Asia, the Middle East, and India as local populations became sufficiently large. Event 2a, The diversification and migration of P-I throughout Asia. Event 2b, Western exploration brought VARV major to South Africa from the Indian subcontinent, which then spread northward to Central Africa and the Horn of Africa (Somali Peninsula). Events 3 and 4, hypothesis A: The diversification of P-II in the New World followed by its reintroduction into Africa; hypothesis B: The diversification of P-II in Africa, followed by the later introduction of one subclade into the New World.
Since we have expressed it in previous articles, one of the strategies to consider in the fight against certain biological virus, will be the development of mutant vaccines, able to adapt itself in simultaneous, complementary and foreseeable way, to viral specific mutations. For it it is basic to know the ontogeny and phylogeny of virus, whose vaccines are going to be make. Although not that aim, a first passage in that sense has been made by : Yu Li, Darin S. Carroll, Shea N. Gardner, et al, when determining the existence of 2 primary clades of the virus of smallpox (VARV, a member of Orthopoxvirus genus, with a single chain of DNA of double chain. The smallpox was responsible for the death of 300-500 millions people in the 20th century), originated of an ancestral virus, carried by african rodents 68.000 years before the present (AAP), depending on which historical registries we use (virus Asian or African), calibrating the molecular clock. Making possible the construction of a robust filogeny of the VARV, analyzing comparativily single nucleótides polymorphisms (SNPs), in sequences of genomes of 47 VARV, isolated in ample geographic distributions.

I) One of the clades (clade primary, mainly of Asian origin, scattered between 1600 to 400 AAP), represents the more severe clinical forms of smallpox -declared eradicated from 1980- with significant frequencies of fatality (up to 30%) in nonvaccinated populations. What agrees with the first descriptions of smallpox pandemics: 400 years after Christ (a.C.), in China. This clade includes isolations coming from East Asia and of central and south Africa. II) the other clade includes the smallpox (alastrim), minor, phenotipically moderate, described in the American continent and isolated of western Africa. The evidences sustain as well that this clade diverged of an existing ancestral VARV between 6300 to 1.400 AAP, having produced : 2 subclades around 800 AAP. Added analyses, however, suggest the divergence of alastrim and mayor smallpox happened recently but. The first descripction of alastrim in the Caribbean, happened in 1860. During the 19th century appeared moderate cases of smallpox with low CFRs (menos de 1 %), seems to be an Asiatic variant of major VARV.

ORIGEN DE lA VIRUELA

Como lo hemos expresado en otros envíos, una de las estrategias a tener en cuenta en la lucha contra ciertos virus biológicos, será el desarrollo de vacunas mutantes, capaces de adecuarse en simultáneo, complementario y previsible modo, a mutaciones virales especificas. Para ello es fundamental conocer la ontogenia y filogenia de virus, cuyas vacunas se vayan a fabricar. Aunque no con ese fin, un primer paso en ese sentido, lo acaban de dar : Yu Li , Darin S. Carroll , Shea N. Gardner et al, al determinar la existencia de 2 clades primarios del virus de la viruela (VARV, un miembro del género Orthopoxvirus, con una cadena única de DNA de doble cadena. La viruela fue responsable de la muerte de 300–500 milones de personas en el siglo 20th), originarios de un virus ancestral, portado por roedores africanos hace 16,000 or 68,000 años antes del presente (AAP), dependiendo de que registros históricos usemos (virus asiáticos o africanos), para calibrar el reloj molecular. Haciendo posible la construcción de una robusta filogenia del VARV, analizando comparativamente polimorfismos únicos de nucleótidos concatenados (SNPs), de secuencias de genomas de 47 VARV, aislados en amplias distribuciones geográficas.

I) Uno de los clades (clade primario, mayormente de procedencia asiática, diseminado entre 1600 a 400 AAP), representa las formas clinicas más severas de viruela -declarada erradicada desde 1980- con significativas frecuencias de fatalidad (hasta 30%) en poblaciones no vacunadas. Lo que coincide con las primeras descripciones de pandemias de viruela : 400 años después de Cristo (dC), en China. Este clade comprende aislamientos procedentes de Asia central-oriental y de Africa central-y del sur. II) el otro clade incluye a la viruela (alastrim), minor, fenotipicamente moderada, descrita en el continente americano y aislada de África occidental. Las evidencias sustentan que este clade divergió de un VARV ancestral existente entre 6300 a 1,400 AAP, habiendo divergido a su vez : 2 subclades hace 800 AAP. Analisis refrendatorios, no obstante, sugieren que la divergencia del alastrim y la viruela mayor ocurrió mas recientemente. La primera descripccion del alastrim en el Caribe, ocurrió en 1860. Durante el siglo 19th brotes moderados de viruela con bajos CFRs (menos del <1%)> africano, serian en realidad una variante asiática del VARV major.

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