The French Armed Forces Virology Unit: A Chronological Record of Ongoing Research on Orthopoxvirus

Abstract

Since the official declaration of smallpox eradication in 1980, the general population vaccination has ceased worldwide. Therefore, people under 40 year old are generally not vaccinated against smallpox and have no cross protection against orthopoxvirus infections. This naïve population may be exposed to natural or intentional orthopoxvirus emergences. The virology unit of the Institut de Recherche Biomédicale des Armées (France) has developed research programs on orthopoxviruses since 2000. Its missions were conceived to improve the diagnosis capabilities, to foster vaccine development, and to develop antivirals targeting specific viral proteins. The role of the virology unit was asserted in 2012 when the responsibility of the National Reference Center for the Orthopoxviruses was given to the unit. This article presents the evolution of the unit activity since 2000, and the past and current research focusing on orthopoxviruses.

Keywords: Lister strain; antivirals; bioterrorism; emergence; genome replication; orthopoxvirus; smallpox; vaccines.

Figure 1

Genetic diversity of poxviruses. Genus in which French National Reference Center-Expert Laboratory for Orthopoxvirus (NRC-EL-OPX) isolates had been identified is highlighted in blue.

Figure 2

Poxvirus infection cases treated at the NRC-EL-OPX. Patients with lesions due to cowpox virus (CPXV) (A,B), orf virus (ORFV) (C), pseudocowpox virus (PCPV) (D) and molluscum contagiosum virus (MCOV) (E) infection. Lesions are located on the face (A,B), on the thumb (C), on the hand (D) and in the back (E).

Figure 3

Bifurcated needle (A). Modified Vaccinia Lister (MVL) genome scheme with localization of deletions within the vaccinia virus (VACV) Lister-107 genome and the positions of the HindIII restriction fragments (B). The numbers in parentheses below the viral genome indicate the approximate locations of MVL deletions previously mapped in the Modified Vaccinia Ankara (MVA) strain relative to the Copenhagen strain (from left to right, according to the nomenclature of Antoine et al. [31]). The actual open reading frames (ORFs) that were deleted in the VACV Lister genome are identified beneath the indicated MVA deletions, and numbered according to Garcel et al. [29]. The roman numeral nomenclature shown under the deleted genomic regions described in Meyer et al. [32].

Figure 4

Crystallographic structures of D4/A20_1-50 and the DNA polymerase of VACV. (A) D4 is depicted in dark green, and A20_1-50 in magenta. In orange and yellow are shown the residues of D4 and A20, respectively, critical for the D4/A20 contact. Residues R167, P173 of D4, and W43 of A20 are indicated; (B) view of the domain organization. The classical palm, thumb, finger, and exonuclease domains of family B polymerase are shown. The various poxvirus-specific structural insertions are depicted in color. Some residues in insert 3 (dark green) were shown to be critical for E9/A20 interaction [71].