Fig. 1. Heterogeneity in the virus replication cycle.
a | Traditional depiction of the viral replication cycle with its series of defined, uniform steps, using human metapneumovirus (HMPV) as an example. HMPV virions bind to a target receptor and fuse with the host cell membrane (step 1). After fusion, viral RNA is replicated in cytoplasmic replication organelles (step 2) and viral proteins are produced and undergo assembly with the viral RNA (step 3). Homogeneous mature virus particles undergo egress through the cellular membrane (step 4). b | Evidence of substantial heterogeneity in the viral replication cycle is accumulating. Entry can be impacted by the presence of post-translational modification of receptors, including glycosylation (step 1). Upon entry, HMPV replication organelles can traffic along actin-containing nanotubes across tight junctions of the lung epithelium3 (step 2). Variation in assembly (step 3) and egress (step 4) lead to the maturation of heterogeneous virus particles from the cell. Similar heterogeneity has been observed in many different viruses.