Viral Pleomorphism: How Virion Structure Guides Infection and Adaptation

Morphological variability in virion size and shape (pleomorphism) is a prominent feature of many pathogenic enveloped viruses, but understanding its biology presents a long-standing challenge. Understanding the role of pleomorphism in viruses requires structural and functional analysis of virions across broad scales, from molecules and cells to animals and populations. The extent of our understanding of viral pleomorphism has hinged on technological advances in viral analysis of increasingly challenging samples, which now approach high-resolution measurements of viral dynamics in animal infections. We review progress in the field by describing both the foundational work and the ensuing characterization of influenza virus pleomorphism over eight decades and then reassessing it through an alternative lens. We argue that virion shape is not a fixed property of a viral strain but rather a dynamic characteristic that varies according to infection environment to improve viral fitness and facilitate persistence. We then describe pleomorphism in other viruses, particularly Mononegavirales, highlighting shared and unique features with influenza virus. We conclude by discussing emerging technological advances promising to answer unresolved questions about the biology of pleomorphism.