Mechanisms Underlying Host Range Variation in Flavivirus: From Empirical Knowledge to Predictive Models

Halabi, Keren; Mayrose, Itay

doi:10.1007/s00239-021-10013-5

Cited by 3 publications

(2 citation statements)

References 117 publications

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“…The high mutational frequency of Flaviviruses in the range of 10 −3 to 10 −5 per replicated nucleotide creates a swarm of mutants which enables the selection of pre-existing quasispecies, as well as the continued selection of mutations to ensure fitness in the current host [60]. It should be noted that trade-offs following adaptation to one host have not always been observed with Flaviviruses [61]. Furthermore, despite the relatively wide host plasticity of many vector-borne viruses, Flaviviruses have adapted to efficiently replicate in rather selective vertebrate hosts, for JEV being birds and pigs.…”

Section: Discussionmentioning

confidence: 99%

Fitness adaptations of Japanese encephalitis virus in pigs following vector-free serial passaging

Marti,

Nater,

Magalhaes

et al. 2024

Preprint

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Japanese encephalitis virus (JEV) is a zoonotic mosquito-transmitted Flavivirus circulating in birds and pigs. In humans, JEV can cause severe viral encephalitis with high mortality. Considering that vector-free direct virus transmission was observed in pigs, JEV introduction into an immunologically naïve pig population could result in a series of direct transmissions disrupting the alternating host cycling between vertebrates and mosquitoes. To assess the potential consequences of such a realistic scenario, we passaged JEV ten times in pigs. This resulted in higherin vivoviral replication, increased shedding, and stronger innate immune responses in pigs. Nevertheless, the viral tissue tropism remained similar and frequency of direct transmission was not enhanced. Next generation sequencing showed single nucleotide deviations in 10% of the genome during passaging. In total, 25 point mutations were selected to reach a frequency of at least 35% in one of the passages. From these, six mutations resulted in amino acid changes located in the precursor of membrane, the envelope, the non-structural 3 and the non-structural 5 proteins. In a competition experiment with two lines of passaging, the mutation M374L in the envelope protein and N275D in the non-structural protein 5 showed a fitness advantage in pigs. Altogether, the interruption of the alternating host cycle of JEV caused a prominent selection of viral quasispecies as well as selection of de novo mutations associated with fitness gains in pigs, albeit without enhancing direct transmission frequency.Author summaryJapanese encephalitis virus (JEV) represents a major health threat in parts of Asia and Oceania. Primary vertebrate hosts are birds and pigs, but human infection also occurs and can cause severe encephalitis with high mortality. Like other Flaviviruses transmitted by insect bites, JEV requires replication in alternating cycles between mosquitoes on one side and birds or pigs on the other side. However, we previously reported that direct transmissions between pigs in absence of mosquitos can occur. Considering the increased risks for such events after the spread of JEV to a new region with immunologically naïve pigs, the present study was performed to understand if and how a series of direct transmissions would promote JEV adaptations to pigs and change virus-host interactions. Pigs infected with JEV passaged ten times showed enhanced clinical symptoms and stronger antiviral immune response, but luckily no increase in direct transmission was observed. Nevertheless, genomic analysis demonstrated a complete change in dominant virus variants, as well as selection of six viral amino acid changes. This indicates that interruptions of the alternating lifestyle of JEV causes a strong evolutionary pressure, which through fitness adaptations can change the viral characteristics.

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Section: Discussionmentioning

confidence: 99%

Fitness adaptations of Japanese encephalitis virus in pigs following vector-free serial passaging

Marti,

Nater,

Magalhaes

et al. 2024

Preprint

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“…This is exemplified by zoonotic coronaviruses and the latest SARS-CoV-2 virus showing receptor orthologs widely distributed in various domestic and wild mammals in which COVID-19 appears. Furthermore, it is clear that viral persistence may be facilitated by a number of macro-ecological characteristics, in turn contributing to variation and a proclivity for specific hosts [10][11][12][13][14][15]. The potential transmission of pathogens currently affecting humans to animal populations has highlighted the need to adopt a One Health approach regarding global health interventions.…”

Section: Introductionmentioning

confidence: 99%

Nanovaccines against Animal Pathogens: The Latest Findings

et al. 2021

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Nowadays, safe and efficacious vaccines represent powerful and cost-effective tools for global health and economic growth. In the veterinary field, these are undoubtedly key tools for improving productivity and fighting zoonoses. However, cases of persistent infections, rapidly evolving pathogens having high variability or emerging/re-emerging pathogens for which no effective vaccines have been developed point out the continuing need for new vaccine alternatives to control outbreaks. Most licensed vaccines have been successfully used for many years now; however, they have intrinsic limitations, such as variable efficacy, adverse effects, and some shortcomings. More effective adjuvants and novel delivery systems may foster real vaccine effectiveness and timely implementation. Emerging vaccine technologies involving nanoparticles such as self-assembling proteins, virus-like particles, liposomes, virosomes, and polymeric nanoparticles offer novel, safe, and high-potential approaches to address many vaccine development-related challenges. Nanotechnology is accelerating the evolution of vaccines because nanomaterials having encapsulation ability and very advantageous properties due to their size and surface area serve as effective vehicles for antigen delivery and immunostimulatory agents. This review discusses the requirements for an effective, broad-coverage-elicited immune response, the main nanoplatforms for producing it, and the latest nanovaccine applications for fighting animal pathogens.

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