Sequelae and Animal Modeling of Encephalitic Alphavirus Infections

Reyna, Rachel A.; Weaver, Scott C.

doi:10.3390/v15020382

Cited by 4 publications

(3 citation statements)

References 81 publications

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“…We observed similar symptoms in our study where fever, headache, nausea, and vomiting were frequently reported. Seizures occurred in 10% of cases which is similar to previous reports [reviewed in (24, 25)]. During the 2010 outbreak of MADV, reported symptoms included fever, headache, vomiting, and diarrhea followed by progression to a neurological disease similar to that observed for EEEV (8).…”

Section: Discussionsupporting

confidence: 86%

Clinical and epidemiological characteristics of Madariaga and Venezuelan equine encephalitis virus infections

Rivera,

Lezcano-Coba,

Galué

et al. 2024

Preprint

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Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, there are limited clinical and epidemiological reports available, and outbreaks are occurring at an increasing frequency. We addressed this gap by analyzing all the available clinical and epidemiological data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 of human alphavirus encephalitis cases were detected in Panama from 1961 to 2023. Here we describe the clinical signs and symptoms and epidemiological characteristics of these cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection when compared to those of other arbovirus infections occurring in the region. Our results highlight the challenges clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.

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Section: Discussionsupporting

confidence: 86%

Clinical and epidemiological characteristics of Madariaga and Venezuelan equine encephalitis virus infections

Rivera,

Lezcano-Coba,

Galué

et al. 2024

Preprint

Self Cite

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“…Alphaviruses are single-stranded positive-sense RNA viruses responsible for causing arthritic and encephalitic diseases worldwide (1) (2) (3). This genus includes arthropod-borne viruses (arboviruses) such as eastern equine encephalitis virus, chikungunya virus (CHIKV), and Mayaro virus.…”

Section: Introductionmentioning

confidence: 99%

The chikungunya virus E1 glycoprotein fusion loop and hinge alter glycoprotein dynamics leading to cell and host specific changes in infectivity

Thannickal,

Battini,

Spector

et al. 2023

Preprint

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Alphaviruses infect both mammals and insects, yet the distinct mechanisms that alphaviruses use to infect different hosts are not well defined. In this study, we characterize CHIKV E1 variants in the fusion loop (E1-M88L) and hinge region (E1-N20Y)in vitroandin vivoto understand how these regions of the E1 glycoprotein contribute to host-specific infection. Through cell culture assays, we found that CHIKV E1-N20Y enhanced infectivity in mosquito cells while the CHIKV E1-M88L variant enhanced virus binding and infectivity in both BHK-21 and C6/36 cells, and led to changes in the virus cholesterol-dependence in BHK-21 cells. Given thesein vitroresults and that residue E1-M88L is in a defined Mxra8 interacting domain, we hypothesized that this residue may be important for receptor usage. However, while the CHIKV E1-M88L variant increased replication in Mxra8-deficient mice compared to WT CHIKV, it was attenuatedin vitroin mouse fibroblasts, suggesting that residue E1-M88 may function in a cell-type dependent manner to alter entry. Finally, using molecular dynamics to understand how potential changes in the E1 glycoprotein may impact the CHIKV glycoprotein E1-E2 complex, we found that E1-M88L and other E1 domain II variants lead to changes in both E1 and E2 dynamics. Taken together, these studies show that key residues in the CHIKV E1 fusion loop and hinge region function through changes in E1-E2 dynamics to facilitate cell- and host-dependent entry.ImportanceArthropod-borne viruses (arboviruses) are significant global public health threats, and their continued emergence around the world highlights the need to understand how these viruses replicate at the molecular level. The alphavirus class II glycoproteins are critical for virus entry in mosquitoes and mammals, yet how these proteins function is not completely understood. Therefore, to address these gaps in our knowledge, it is critical to dissect how distinct glycoprotein domains functionin vitroandin vivo. Here, we show that changes in the CHIKV E1 fusion loop and hinge contribute to host-specific entry and E1-E2 dynamics, furthering our knowledge of how alphaviruses infect mammals and insects.

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“… 51 , 54 Using these models, VEEV cellular tropism and routes of infection leading to neuroinvasion and encephalitis have been studied. 55 – 57 …”

Section: Introductionmentioning

confidence: 99%

Entry receptor LDLRAD3 is required for Venezuelan equine encephalitis virus peripheral infection and neurotropism leading to pathogenesis in mice

Kafai,

Janova,

Cain

et al. 2023

Cell Reports

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Sequelae and Animal Modeling of Encephalitic Alphavirus Infections

Cited by 4 publications

References 81 publications

Clinical and epidemiological characteristics of Madariaga and Venezuelan equine encephalitis virus infections

Clinical and epidemiological characteristics of Madariaga and Venezuelan equine encephalitis virus infections

The chikungunya virus E1 glycoprotein fusion loop and hinge alter glycoprotein dynamics leading to cell and host specific changes in infectivity

Entry receptor LDLRAD3 is required for Venezuelan equine encephalitis virus peripheral infection and neurotropism leading to pathogenesis in mice

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