Collective Infectious Units in Viruses

Abstract

Increasing evidence indicates that viruses do not simply propagate as independent virions among cells, organs, and hosts. Instead, viral spread is often mediated by structures that simultaneously transport groups of viral genomes, such as polyploid virions, aggregates of virions, virion-containing proteinaceous structures, secreted lipid vesicles, and virus-induced cell-cell contacts. These structures increase the multiplicity of infection, independently of viral population density and transmission bottlenecks. Collective infectious units may contribute to the maintenance of viral genetic diversity, and could have implications for the evolution of social-like virus-virus interactions. These may include various forms of cooperation such as immunity evasion, genetic complementation, division of labor, and relaxation of fitness trade-offs, but also noncooperative interactions such as negative dominance and interference, potentially leading to conflict.

Keywords: Baculoviruses; Genetic diversity; Microvesicles; Multiplicity of infection; Polyploid virion; Social evolution.

Fig. 1. Structure of collective infectious units in viruses.

(A) Viral capsids can contain one or multiple genome copies, producing n-ploid virions. Filamentous capsids probably have increased tendency to accommodate multiple genomes copies, but polyploidy has also been described in icosahedral capsids. A diploid icosahedral virion is represented. (B) Aggregation is a commonly described process in virion preparations. However, its molecular basis and physiological relevance remain largely unassessed. Aggregation of bullet-shaped virions is shown, indicating hypothetical virion surface molecules that may mediate specific virion-virion contacts. (C) Occlusion bodies (OBs) are virions encased in crystallized polyhedrin and constitute the inter-host transmission structure of baculoviruses. Crystals are dissolved under the alkaline pH of the larval midgut, releasing occlusion-derived virions (ODVs). In turn, these can be single virions (single nucleopolyhedroviruses) or groups of virions (multiple nucleopolyhedroviruses). (D) Virion-containing lipid vesicles include exosome-like vesicles (which can contain full virions or viral RNA) and autophagosome-like vesicles. These are rich in phosphatidylserine, which stimulates phagocytosis and thus potentiates viral entry. (E) Cell-to-cell transmission also ensures that multiple viral genome copies are collectively delivered to the same target cell. Use of plasmodesmata (PD) by plant viruses is depicted as an example. Whereas normal PDs are too small to allow viral passage and contain smooth endoplasmic reticulum, plant viruses encode a movement protein (MP) that promotes cell-to-cell transmission by altering the structure of PDs.

Fig. 2. Possible social-like interactions mediated by collective infectious units in viruses.

(A) Co-infection of cells with multiple viral genomes may increase their ability to evade innate immunity responses. Upon viral entry, pathogen-associated molecular patterns (proteins, DNA/RNA, etc.) are sensed by the cell and trigger an antiviral state controlled by immunity effectors. By increasing the cellular MOI, the virus may overwhelm these responses and more successfully complete the infection cycle. Orange bars: genome copies; orange triangles, ellipses and rectangles: viral products; green: cellular responses to infection. CIU: collective infectious unit. (B) Different genetic variants of a virus may complement each other when present in the same cell. Two deleterious mutants (orange and red) mapping to different viral genes are represented. Normal viral genes and proteins are represented in blue. Whereas genetic complementation requires that different loci are involved, other forms of heterotypic cooperation can be envisaged that could involve the same locus, including synergistic interactions between beneficial mutations, or division of labor. For instance, in multifunctional proteins, co-infecting variants may specialize in subsets of these functions. (C) Negative dominance as an example of interference, a non-cooperative virus-virus interaction. Negative dominance is particularly likely in oligomeric structures (here, a capsid). By forming mixed oligomers, a deleterious variant (orange filled) interferes with the wild-type variant (wt, white filled). Other forms of non-cooperative interactions have been described, as exemplified by DIPs, which act as social cheats.