Global Alert and Response (GAR)

Abstracts summarizing recent research overseen by the WHO Advisory Committee on Variola Virus Research - 2004

Clues to Variola Virus Evolution and Virulence Changes

Joseph J. Esposito1#, Scott A. Sammons1, A. Michael Frace1, John D. Osborne1, Melissa Olsen-Rasmussen1, Ming Zhang1, Renee Galloway1, Inger K. Damon2, Richard L. Kline2, Yu Li2, Joanne L. Patton2, James W. LeDuc3, Robert M. Wohlhueter1

1 Biotechnology Core Facility Branch, Scientific Resources Program
2Poxvirus Activity,
3 Division of Viral and Rickettsial Diseases
National Center for Infectious Diseases,
Centers for Disease Control and Prevention, Atlanta, Georgia, 30333, United States of America

# Please direct all queries to corresponding author

Ironically, as we celebrate the 25th anniversary of smallpox eradication, the etiologic agent variola virus remains. We are investigating the evolution and sequence diversity of an epidemiologically varied selection of 48 variola virus isolates from the last 40 years that smallpox was endemic. The isolates’ group into three strains: West African major, American alastrim minor, and Asian major, the latter group contains non-West-African African major and minor variants.

Assessment of lineage-specific gene/sequence loss and negative selection in the ~186-kilobase pair genome DNA, phylogenetic relationships with other orthopoxviruses, and exclusion of the minor variola strains and variants because they emerged in the late 1800’s infer the lineage of the selected isolates derives from the West African major strain. Small differences in a consensus of 13 of ~200 potential encoded proteins distinguish the non-West-African African major and minor variants and small differences in 41 putative proteins distinguish West African from alastrim strains, which may have undergone recombination after they diverged from each other.

Variola virus sequence diversity data should help improve viral detection accuracy, antiviral drug targeting, and systems to develop and assess safe, unfailing cures to supplant smallpox era remedies if variola virus somehow reemerges.

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