A vital gene for modified vaccinia virus Ankara replication in human cells.

Vaccinia virus (VACV), the prototype orthopoxvirus, is the first live viral vaccine used to protect against smallpox, one of the most feared infectious diseases of humans (1). This outstanding achievement was possible because even as the various orthopoxviruses evolved and diversified they often retained major parts of their virion composition in common. In consequence, productive infection with one orthopoxvirus, VACV, effectively immunizes the host against infection by other orthopoxviruses including variola virus, the closely related agent of smallpox. Successful vaccination against smallpox positively correlated with the productive replication of VACV in the skin of vaccinated individuals. However, on occasion the inoculation of live VACV had risk because the vaccine virus could develop generalized infections and cause other severe adverse events following vaccination (2). Ever since, research with VACV seeks to elucidate the many secrets of this unique virus–human host interaction. What makes VACV efficiently grow in human cells? This might sound like a simple question since the growth tropism of many other viruses is largely determined by the binding of a specific viral protein (ligand) to its host cell counterpart (receptor) for successful entry. In contrast, the host tropism of VACV and poxviruses, in general, is far more complex and wonderful with numerous, postentry, intracellular events dictating whether productive virus replication will occur at the level of the host cell, the tissue, or the whole organism (3). VACV can readily bind to and enter many different cells from diverse animal species. After entry, however, successful VACV replication in a specific host cell depends on the functional activity of an appropriate subset of viral genes, the so-called host-range genes, predicted to control the intracellular host defenses at various levels. In PNAS, Peng and Moss (4) identify and explore a previously unknown viral protein as a major facilitator of VACV growth in … [↵][1]1Email: gerd.sutter{at}lmu.de. [1]: #xref-corresp-1-1