Abstract
BackgroundWithin-host competition between strains of a vector-borne pathogen can affect strain frequencies in both the host and vector, thereby affecting viral population dynamics. However little is known about inter-strain competition in one of the most genetically diverse and epidemiologically important mosquito-borne RNA virus: dengue virus (DENV). To assess the strength and symmetry of intra-host competition among different strains of DENV, the effect of mixed infection of two DENV serotypes, DENV2 and DENV4, on the replication of each in cultured mosquito cells was tested. The number of infectious particles produced by each DENV strain in mixed infections was compared to that in single infections to determine whether replication of each strain was decreased in the presence of the other strain (i.e., competition). The two DENV strains were added to cells either simultaneously (coinfection) or with a 1 or 6-hour time lag between first and second serotype (superinfection).ResultsDENV2 and DENV4 showed significantly reduced replication in mixed infection relative to single infection treatments. In superinfection treatments, replication was suppressed to a greater extent when the interval between addition of each strain was longer, and when a strain was added second. Additionally, competitive effects were asymmetric: although both strains replicated to similar peak population sizes in single infections, DENV2 was more suppressed than DENV4 in mixed infections. Superinfection treatments yielded significantly lower combined virus titers than coinfection or single infection treatments.ConclusionCompetition between DENV strains in cultured mosquito cells can cause a significant decrease in peak viral population sizes, which could translate to decreased transmission by the vector. Effects of competition were asymmetric between DENV2 and DENV4, probably reflecting significant variation in the competitive ability of DENV strains in nature. Competition was strongest in superinfection treatments, suggesting that colonization of new DENV strains could be impeded in areas where numerous mosquitoes are infected with endemic DENV strains.
Highlights
Within-host competition between strains of a vector-borne pathogen can affect strain frequencies in both the host and vector, thereby affecting viral population dynamics
To test whether the replication of a single serotype infecting at a multiplicity of infection (MOI) of 5 was suppressed by an equal dose of the same serotype, we compared the replication of each serotype in a single infection (MOI 5) with its replication after superinfection by the same serotype 1 or 6 hours following the initial infection (MOI 5 + MOI 5 = 10)
Each serotype reached significantly higher titers on average at each timepoint when superinfected by the same serotype (Fig. 1, Table 2, left; [Additional File 1]), suggesting that single infections at MOI 5 have not exhausted the potential for host cells to support virus replication, and that serotypes in mixed infections had the potential to grow to titers as high as those in their respective single
Summary
Within-host competition between strains of a vector-borne pathogen can affect strain frequencies in both the host and vector, thereby affecting viral population dynamics. To assess the strength and symmetry of intra-host competition among different strains of DENV, the effect of mixed infection of two DENV serotypes, DENV2 and DENV4, on the replication of each in cultured mosquito cells was tested. Infection of a single host by multiple strains of a pathogen may result in competition for host resources [1] Such intra-host competition is predicted to shape a variety of pathogen traits such as virulence, transmissibility, and resource partitioning, that could affect epidemiology and virus population dynamics [2,3,4,5,6,7,8,9]. In order to understand and predict the evolutionary epidemiology of medically important viruses that exist as mixed-strain assemblages, it is important to study the interactions within those particular systems
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