Identification and characterization of two nonessential regions of the rabbitpox virus genome involved in virulence

We have developed a means to identify genes associated with particular aspects of virulence. By beginning with an avirulent deletion mutant of rabbitpox virus and systematically reintroducing overlapping segments of the deleted region, we have identified two regions of the viral genome associated with increased virulence in mice. Evaluation of illness has been aided by the exploitation of weight loss as an indicator of pathogenesis. One of the regions identified by this method contains several open reading frames and includes two previously described genes. A third, as yet undescribed, gene within this region potentially encodes a product related to the C5 protein of human complement. The second region of DNA associated with increased virulence is the HindIII M fragment, which contains only one complete open reading frame. Analysis of this previously unreported gene shows coding potential for a polypeptide of 254 amino acids (approximately 25 kDa) which is related to the C4 component of human complement. The elucidation of two new viral genes related to complement components, taken together with the recent report of the biological activity of a poxvirus-encoded complement-binding protein, suggests the importance of interactions of the virus with the complement system during a normal infection.