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Cover Illustration: The N1L protein of vaccinia and variola (Smallpox) viruses is critical for virus survival and propagation within host cells. The crystal structure of N1L (upper stereo pair) reveals a striking homology to host proteins of the Bcl-2 family (compared in lower pair), which regulate apoptosis, or programmed cell death, a host defense mechanism against pathogens. In vitro binding studies support a direct role for N1L in modulating apoptosis, a finding that should provide new leads for the development of antiviral therapies and vaccines to treat a future Smallpox outbreak. (See Aoyagi et al., pp. 118–124.)