Poxvirus membrane biogenesis

Abstract

Poxviruses differ from most DNA viruses by replicating entirely within the cytoplasm. The first discernible viral structures are crescents and spherical immature virions containing a single lipoprotein membrane bilayer with an external honeycomb lattice. Because this viral membrane displays no obvious continuity with a cellular organelle, a de novo origin was suggested. Nevertheless, transient connections between viral and cellular membranes could be difficult to resolve. Despite the absence of direct evidence, the intermediate compartment (ERGIC) between the endoplasmic reticulum (ER) and Golgi apparatus and the ER itself were considered possible sources of crescent membranes. A break-through in understanding poxvirus membrane biogenesis has come from recent studies of the abortive replication of several vaccinia virus null mutants. Novel images showing continuity between viral crescents and the ER and the accumulation of immature virions in the expanded ER lumen provide the first direct evidence for a cellular origin of this poxvirus membrane.

Keywords: Endoplasmic reticulum; Vaccinia virus; Viral membrane proteins; Virus morphogenesis.

Fig. 1

Transmission electron microscopic image of a HeLa cell infected with VACV. Abbreviations: MV, mature virion; IV, immature virion; WV, wrapped virion; EV, extracellular enveloped virion; n, IV with nucleoid. Scale bar at bottom. Provided by A. Weisberg.

Fig. 2

Transmission electron microscopic image of a cell infected with VACV showing IVs forming within a virus factory. Free ends, lipoprotein membrane and D13 scaffold are labeled with arrows. Scale bar at bottom. Provided by A. Weisberg.

Fig. 3

Transmission electron microscopic images of a BS-C-1 cell infected with a VACV L2 deletion mutant showing dense inclusions. Arrows point to short crescents. V, dense inclusion of viroplasm. Inset, high magnification of portion of inclusion. Scale bars shown. Adapted from (Maruri-Avidal et al., 2013a)

Fig. 4

Transmission electron microscopic images of cells infected with a VACV L2 and A30.5 deletion mutants showing association of ER and IV-like structures. (A, B) VACV L2 deletion mutant infection of BS-C-1 cells. (C–F) VACV A30.5 deletion mutant infection of RK-13 cells. Arrows, membrane with spicule layer; Arrowheads, smooth membrane. Scale bars shown. Adapted from (Maruri-Avidal et al., 2013c).

Fig. 5

Model for formation of viral membranes during infection with wild-type (WT) and mutant VACV. L2, A30.5, A11, A17, A14 and D13 refer to VACV proteins; ΔL2, ΔA30.5 and ΔA11 refer to VACV deletion mutants. Adapted from (Maruri-Avidal et al., 2013c).