The Coat Protein and NIa Protease of Two Potyviridae Family Members Independently Confer Superinfection Exclusion

Abstract

Superinfection exclusion (SIE) is an antagonistic virus-virus interaction whereby initial infection by one virus prevents subsequent infection by closely related viruses. Although SIE has been described in diverse viruses infecting plants, humans, and animals, its mechanisms, including involvement of specific viral determinants, are just beginning to be elucidated. In this study, SIE determinants encoded by two economically important wheat viruses, Wheat streak mosaic virus (WSMV; genus Tritimovirus, family Potyviridae) and Triticum mosaic virus (TriMV; genus Poacevirus, family Potyviridae), were identified in gain-of-function experiments that used heterologous viruses to express individual virus-encoded proteins in wheat. Development of reverse genetics systems for viruses has revolutionized the understanding of viral replication, infection, and disease development through identification of viral determinants involved in these processes as well as the elucidation of interactions between viral and host factors (1-3). However, virusvirus interactions in hosts that facilitate superinfection exclusion (SIE) between related viruses or synergistic interactions between unrelated viruses have received less attention (4, 5). Synergistic interactions are facilitative virus-virus interactions between two or more unrelated viruses, and these interactions often cause increased virus accumulation of one or both viruses that could lead to severe disease compared to infection by individual viruses (4). In contrast, SIE is the result of antagonistic virus-virus interactions between closely related viruses (5-7).SIE, often referred to as "cross-protection" or "homologous interference," is defined as the phenomenon whereby initial infection by one virus prevents subsequent infection of preinfected cells by closely related viruses. SIE was originally observed between two strains of Tobacco mosaic virus (TMV) (6, 7), followed by observations with bacteriophages (8, 9). In TMV, cross-protection was used to examine the relatedness of newly collected virus isolates as being strains of, or distinct from, existing virus isolates (7, 10). Subsequently, cross-protection has been used for the management of plant viruses by purposefully infecting plants with mild isolates of a virus to prevent infection by severe isolates (11,12).The SIE phenomenon has been observed in diverse groups of plant-, human-, and animal-infecting viruses belonging to the reverse transcribing viruses such as Human immunodeficiency virus

Rescue of Tomato spotted wilt tospovirus entirely from cDNA clones, establishment of the first reverse genetics system for a segmented (-)RNA plant virus

“…However, high expression of either N or RdRp results in cell death and cause negative effects on the replication and transcription of TSWV. Moreover, ectopic expression of N and RdRp by the strong 35S promoter also seems to cause superinfection exclusion, as earlier observed and reported with various viruses infecting humans, animals, and plants (47, 58–60). During superinfection exclusion a preexisting infection of virus prevents a secondary infection with the same or a highly similar virus.…”

“…It is an active virus-controlled process that may be determined by a specific viral protein. For example, for potyvirus the coat protein and NIa protease have been identified to control superinfection exclusion (60). For TCV, the p28, involved in replication protein, was shown to confer superinfection exclusion as a priori expression of p28 blocked (re-)infection with TCV (47).…”

Virus Population Bottlenecks: What Are They Telling Us?

“…The very fact that the each of the cell clusters contained a single variant betrays highly stringent population bottlenecks that permitted just one variant to infect a group of connected cells in an SL. Strikingly similar observations have since been made with other viruses, including WSMV, apple latent spherical virus (ALSV), tobacco etch virus (TEV), and a negative-strand RNA virus known as sonchus yellow net virus (SYNV) [29][30][31][32][33] , underlining the highly conserved nature of intracellular bottlenecking encountered by virus populations.…”

“…It is also well known that established infections exclude secondary invasions by the same virus 7,[38][39][40] . Finally, such exclusion/repression has been shown to be actively enforced by virus-encoded proteins in several cases 30,31,34 . Why would viruses actively block most copies of their own genomes from replicating in the same cell?…”

The Matrix Protein of a Plant Rhabdovirus Mediates Superinfection Exclusion by Inhibiting Viral Transcription

“…For example, when GFP-and RFP-labeled plum pox virus derivatives were coinoculated onto plants, the fluorescent markers demonstrated that the two viruses coexisted in the same plant leaves but showed that they occupied largely nonoverlapping cell clusters (26). Similar spatial separation or mutual exclusion between variants of the same virus have been observed for apple latent spherical virus and bean yellow mosaic virus (27,28), TMV (29,30), soilborne wheat mosaic virus (31), wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV) (32), and turnip crinkle virus (TCV) (33). However, when these differently tagged viruses were inoculated sequentially, the primary virus infection completely blocked subsequent infection by the secondary invader at the whole-plant level (34)(35)(36)(37)(38)(39)(40)(41).…”