Exploring the inside details of virions by electron microscopy

Spherical virions can be structurally divided into two compositions: the outer protein shell, and its content including the viral genome and enzymes. Three-dimensional virus structures are the key to understanding the virus life cycles and their mechanisms for infecting hosts, which can contribute to anti-viral drug design. These structures can be solved either by X-ray crystallization (Harrison et al. 1978) or by cryo-electron microscopy (cryo-EM) (Dubochet et al. 1988), or by combining both methods (Guu et al. 2009). In retrospect, the X-ray method had begun to solve viral structures at high resolution with atomic information since the late 1970s (Harrison et al. 1978; Abad-Zapatero et al. 1980), while cryo-EM, considered as a blobology method, only provided low- or medium-resolution information from the 1980s (Dubochet et al. 1988). In recent years, cryo-EM has emerged to rival with X-ray on the high-resolution structure determination of spherical viruses (Grant and Grigorieff 2015; Liu et al. 2016). In spite of a wealth of virus structures determined by these methods, the solved parts were limited to the viral capsid, while the remaining moieties, like the viral genomes and virus-self-functional enzymes within, were rarely visualized. Strikingly, in a recent paper published in Science (Liu and Cheng 2015), Drs. Liu and Cheng managed to discern the full genome and polymerase of cytoplasmic polyhedrosis virus (CPV), using their new approach adapted from traditional single-particle analysis of icosahedral viruses.