Articles of Significant Interest Selected from This Issue by the Editors
Newly Discovered Viruses Reveal the Diversity and Evolutionary History of the Flaviviridae and Related Viruses
Although flaviviruses are important pathogens of humans and animals, knowledge of their biodiversity is largely limited to those infecting mammalian hosts and their arthropod vectors. Shi et al. (p. 659–669) investigated a diverse group of arthropod and vertebrate species not previously included in flavivirus surveillance programs. The viruses discovered fill major gaps in the phylogenetic diversity of the Flaviviridae, highlighting large-scale changes in genome structure, genome size, and replication strategy during viral evolution. This study provides a new understanding of the diversity, host range, and evolution of flaviviruses and their relatives.
Diversity of previously described and newly discovered members of the Flaviviridae and related viruses.
Extracellular Vesicles Mediate Transmission of a New Tick-Borne Bunyavirus
Severe fever with thrombocytopenia syndrome (SFTS) virus is an emergent tick-borne bunyavirus that has been isolated from patients presenting with hemorrhagic manifestations. Silvas et al. (p. 873–886) report the presence of virus-like particles within extracellular vesicles produced by cells infected with SFTS virus. These “infectious” extracellular vesicles are capable of maintaining SFTS virus replication even in the presence of neutralizing antibodies. This work represents a significant contribution to an understanding of how SFTS virus hijacks vesicular transport to establish infection and points toward a new mechanism for virus replication among arthropod-borne viruses.
Extracellular vesicles harbor infectious SFTS virus-like particles.
Cell-Free Assembly of Infectious Human Papillomavirus Pseudovirions
Human papillomaviruses (HPVs) are challenging to cultivate. Cerqueira et al. (p. 1096–1107) developed a cell-free system to study HPV16 assembly and genome packaging. The results suggest a size discrimination mechanism for genome encapsidation whereby the virion proteins randomly attempt to package nuclear DNA through iterative rounds of partial assembly and disassembly. Encounter of a DNA molecule that is small enough to be entirely encapsidated, e.g., the viral genome, results in formation of a stable complex that is no longer subject to disassembly. This knowledge enhances an understanding of HPV assembly, which should illuminate new targets for antiviral agents and accelerate development of improved papillomavirus gene transfer vectors.
Model of HPV16 assembly.
Structure and Function of the N-Terminal Domain of the Vesicular Stomatitis Virus RNA Polymerase
Nonsegmented negative-strand RNA viruses share a common set of functionally conserved proteins that are essential for viral transcription, including the RNA-dependent RNA polymerase (L). Qiu et al. (p. 715–724) determined the crystal structure of the N-terminal domain of the L protein (LNTD) from vesicular stomatitis virus (VSV). The structure shows that conserved amino acid residues among the L proteins of the Mononegavirales cluster in a single site on the domain surface; mutation of residues in this location compromises polymerase function. This site could be a useful target for the design of new therapeutics against negative-strand RNA viruses.
Surface representation of the VSV LNTD showing localization of amino acid conservation.
Tree Shrew Trigeminal Ganglion Infection by Herpes Simplex Virus 1
Mice and rabbits have been used to study acute and recurrent disease caused by herpes simplex virus 1 (HSV-1). Mice, although an economical model, do not mimic some aspects of the human disease, such as spontaneous reactivation and shedding from infected eyes. Furthermore, HSV-1 kills neurons in the peripheral nervous system during acute infection of mice, yet recurrent HSV-1 infections in humans do not compromise sensation. Li et al. (p. 790–804) show that tree shrews infected with HSV-1 exhibit spontaneous shedding of virus in eye tears and develop minimal damage to sensory ganglia during acute infection. However, HSV-1 establishes latency in both the peripheral and central nervous system in these animals, thus establishing a new small animal model for studies of HSV-1 pathogenesis.
HSV-1 titers in mouse and tree shrew trigeminal ganglia during acute infection (photo by Longbao Lyu, Kunming Institute of Zoology).
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