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Loss of Cytoskeletal Transport during Egress Critically Attenuates Ectromelia Virus Infection In Vivo

journal contribution
posted on 2023-05-18, 18:19 authored by Lynn, H, Horsington, J, Ter, LK, Han, S, Chew, YL, Diefenbach, RJ, Way, M, Chaudhri, G, Gunasegaran KarupiahGunasegaran Karupiah, Newsome, TP
Egress of wrapped virus (WV) to the cell periphery following vaccinia virus (VACV) replication is dependent on interactions with the microtubule motor complex kinesin-1 and is mediated by the viral envelope protein A36. Here we report that ectromelia virus (ECTV), a related orthopoxvirus and the causative agent of mousepox, encodes an A36 homologue (ECTV-Mos-142) that is highly conserved despite a large truncation at the C terminus. Deleting the ECTV A36R gene leads to a reduction in the number of extracellular viruses formed and to a reduced plaque size, consistent with a role in microtubule transport. We also observed a complete loss of virus-associated actin comets, another phenotype dependent on A36 expression during VACV infection. ECTV ΔA36R was severely attenuated when used to infect the normally susceptible BALB/c mouse strain. ECTV ΔA36R replication and spread from the draining lymph nodes to the liver and spleen were significantly reduced in BALB/c mice and in Rag-1-deficient mice, which lack T and B lymphocytes. The dramatic reduction in ECTV ΔA36R titers early during the course of infection was not associated with an augmented immune response. Taken together, these findings demonstrate the critical role that subcellular transport pathways play not only in orthopoxvirus infection in an in vitro context but also during orthopoxvirus pathogenesis in a natural host. Furthermore, despite the attenuation of the mutant virus, we found that infection nonetheless induced protective immunity in mice, suggesting that orthopoxvirus vectors with A36 deletions may be considered another safe vaccine alternative.

History

Publication title

Journal of Virology (Online)

Volume

86

Issue

13

Pagination

7427-7443

ISSN

1098-5514

Department/School

Tasmanian School of Medicine

Publisher

American Society for Microbiology

Place of publication

United States

Rights statement

Copyright 2012 American Society for Microbiology

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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