Dataset Information

Age-structured vectorial capacity reveals timing, not magnitude of within-mosquito dynamics is critical for arbovirus fitness assessment.

ABSTRACT:

Background

Transmission dynamics of arboviruses like Zika virus are often evaluated by vector competence (the proportion of infectious vectors given exposure) and the extrinsic incubation period (EIP, the time it takes for a vector to become infectious), but vector age is another critical driver of transmission dynamics. Vectorial capacity (VC) is a measure of transmission potential of a vector-pathogen system, but how these three components, EIP, vector competence and vector age, affect VC in concert still needs study.

Methods

The interaction of vector competence, EIP, and mosquito age at the time of infection acquisition (Age_acquisition) was experimentally measured in an Aedes aegypti-ZIKV model system, as well as the age-dependence of probability of survival and the willingness to bite. An age-structured vectorial capacity framework (VC_age) was then developed using both EIP_Min and EIP_Max, defined as the time to first observed minimum proportion of transmitting mosquitoes and the time to observed maximum proportion of transmitting mosquitoes.

Results

The within-mosquito dynamics of vector competence/EIP were not significant among treatments where mosquitoes were exposed at different ages. However, VC_age revealed: (i) age-dependence in vector-virus interactions is important for transmission success; (ii) lower vector competence but at shorter EIPs was sufficient for transmission perpetuation; and (iii) R₀ may be overestimated by using non-age-structured VC.

Conclusions

The results indicate that ultimately the temporal component of the virus-vector dynamics is most critical, especially when exposure occurred at advanced mosquito age. While our study is limited to a single virus-vector system, and a multitude of other factors affect both vector competence and mosquito mortality, our methods can be extrapolated to these other scenarios. Results indicate that how 'highly' or 'negligibly' competent vectors are categorized may need adjustment.

SUBMITTER: Mayton EH

PROVIDER: S-EPMC7296759 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Age-structured vectorial capacity reveals timing, not magnitude of within-mosquito dynamics is critical for arbovirus fitness assessment.

Mayton E Handly EH Tramonte A Ryan AR Wearing Helen J HJ Christofferson Rebecca C RC

Parasites & vectors 20200615 1

<h4>Background</h4>Transmission dynamics of arboviruses like Zika virus are often evaluated by vector competence (the proportion of infectious vectors given exposure) and the extrinsic incubation period (EIP, the time it takes for a vector to become infectious), but vector age is another critical driver of transmission dynamics. Vectorial capacity (VC) is a measure of transmission potential of a vector-pathogen system, but how these three components, EIP, vector competence and vector age, affect ...[more]

PMID: 32539759

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Project description:Vectorial capacity and the basic reproductive number (R(0)) have been instrumental in structuring thinking about vector-borne pathogen transmission and how best to prevent the diseases they cause. One of the more important simplifying assumptions of these models is age-independent vector mortality. A growing body of evidence indicates that insect vectors exhibit age-dependent mortality, which can have strong and varied affects on pathogen transmission dynamics and strategies for disease prevention.Based on survival analysis we derived new equations for vectorial capacity and R(0) that are valid for any pattern of age-dependent (or age-independent) vector mortality and explore the behavior of the models across various mortality patterns. The framework we present (1) lays the groundwork for an extension and refinement of the vectorial capacity paradigm by introducing an age-structured extension to the model, (2) encourages further research on the actuarial dynamics of vectors in particular and the relationship of vector mortality to pathogen transmission in general, and (3) provides a detailed quantitative basis for understanding the relative impact of reductions in vector longevity compared to other vector-borne disease prevention strategies.Accounting for age-dependent vector mortality in estimates of vectorial capacity and R(0) was most important when (1) vector densities are relatively low and the pattern of mortality can determine whether pathogen transmission will persist; i.e., determines whether R(0) is above or below 1, (2) vector population growth rate is relatively low and there are complex interactions between birth and death that differ fundamentally from birth-death relationships with age-independent mortality, and (3) the vector exhibits complex patterns of age-dependent mortality and R(0) ? 1. A limiting factor in the construction and evaluation of new age-dependent mortality models is the paucity of data characterizing vector mortality patterns, particularly for free ranging vectors in the field.

Project description:Infected hosts possess two alternative strategies to protect themselves against the negative impact of virus infections: resistance, used to abrogate virus replication, and disease tolerance, used to avoid tissue damage without controlling viral burden. The principles governing pathogen resistance are well understood, while less is known about those involved in disease tolerance. Here, we studied bluetongue virus (BTV), the cause of bluetongue disease of ruminants, as a model system to investigate the mechanisms of virus-host interactions correlating with disease tolerance. BTV induces clinical disease mainly in sheep, while cattle are considered reservoirs of infection, rarely exhibiting clinical symptoms despite sustained viremia. Using primary cells from multiple donors, we show that BTV consistently reaches higher titers in ovine cells than cells from cattle. The variable replication kinetics of BTV in sheep and cow cells were mostly abolished by abrogating the cell type I interferon (IFN) response. We identified restriction factors blocking BTV replication, but both the sheep and cow orthologues of these antiviral genes possess anti-BTV properties. Importantly, we demonstrate that BTV induces a faster host cell protein synthesis shutoff in primary sheep cells than cow cells, which results in an earlier downregulation of antiviral proteins. Moreover, by using RNA sequencing (RNA-seq), we also show a more pronounced expression of interferon-stimulated genes (ISGs) in BTV-infected cow cells than sheep cells. Our data provide a new perspective on how the type I IFN response in reservoir species can have overall positive effects on both virus and host evolution. IMPORTANCE The host immune response usually aims to inhibit virus replication in order to avoid cell damage and disease. In some cases, however, the infected host avoids the deleterious effects of infection despite high levels of viral replication. This strategy is known as disease tolerance, and it is used by animal reservoirs of some zoonotic viruses. Here, using a virus of ruminants (bluetongue virus [BTV]) as an experimental system, we dissected virus-host interactions in cells collected from species that are susceptible (sheep) or tolerant (cow) to disease. We show that (i) virus modulation of the host antiviral type I interferon (IFN) responses, (ii) viral replication kinetics, and (iii) virus-induced cell damage differ in tolerant and susceptible BTV-infected cells. Understanding the complex virus-host interactions in disease tolerance can allow us to disentangle the critical balance between protective and damaging host immune responses.

Dataset Information

Age-structured vectorial capacity reveals timing, not magnitude of within-mosquito dynamics is critical for arbovirus fitness assessment.

Background

Methods

Results

Conclusions

Publications

Age-structured vectorial capacity reveals timing, not magnitude of within-mosquito dynamics is critical for arbovirus fitness assessment.

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