#Host #nutritional status affects #alphavirus #virulence, #transmission, and #evolution (PLOS Pathog., abstract)

[Source: PLoS Pathogens, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Host nutritional status affects alphavirus virulence, transmission, and evolution

James Weger-Lucarelli , Lucia Carrau, Laura I. Levi, Veronica Rezelj, Thomas Vallet, Hervé Blanc, Jérémy Boussier, Daniela Megrian, Sheryl Coutermarsh-Ott, Tanya LeRoith, Marco Vignuzzi

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Published: November 11, 2019 / DOI: https://doi.org/10.1371/journal.ppat.1008089 / This is an uncorrected proof.

 

Abstract

Malnourishment, specifically overweight/obesity and undernourishment, affects more than 2.5 billion people worldwide, with the number affected ever-increasing. Concurrently, emerging viral diseases, particularly those that are mosquito-borne, have spread dramatically in the past several decades, culminating in outbreaks of several viruses worldwide. Both forms of malnourishment are known to lead to an aberrant immune response, which can worsen disease outcomes and reduce vaccination efficacy for viral pathogens such as influenza and measles. Given the increasing rates of malnutrition and spread of arthropod-borne viruses (arboviruses), there is an urgent need to understand the role of host nutrition on the infection, virulence, and transmission of these viruses. To address this gap in knowledge, we infected lean, obese, and undernourished mice with arthritogenic arboviruses from the genus Alphavirus and assessed morbidity, virus replication, transmission, and evolution. Obesity and undernourishment did not consistently influence virus replication in the blood of infected animals except for reductions in virus in obese mice late in infection. However, morbidity was increased in obese mice under all conditions. Using Mayaro virus (MAYV) as a model arthritogenic alphavirus, we determined that both obese and undernourished mice transmit virus less efficiently to mosquitoes than control (lean) mice. In addition, viral genetic diversity and replicative fitness were reduced in virus isolated from obese compared to lean controls. Taken together, nutrition appears to alter the course of alphavirus infection and should be considered as a critical environmental factor during outbreaks.

 

Author summary

Over- and undernutrition, collectively known as malnutrition, affect over 2.5 billion people worldwide. Associations between malnutrition and mosquito-borne virus infection and resulting disease have been identified in epidemiological studies but have not been explored in controlled studies. Here, we infect obese or undernourished mice with different arthritis inducing viruses in the genus Alphavirus and measure disease symptoms, viral replication, transmission, and evolution. We found that markers of disease, namely weight loss and footpad swelling, were increased in obese mice. We also found that replication differences between mice fed different diets were minimal except late in infection for obese mice when levels of virus dropped significantly. When mosquitoes were allowed to feed on mice fed different diets, we observed reduced infection and transmission rates, depending on the diet. Finally, we found reduced genetic diversity and replicative fitness of virus isolated from obese mice. This study provides insights into the influence of nutrition on alphavirus pathogenesis and evolution.

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Citation: Weger-Lucarelli J, Carrau L, Levi LI, Rezelj V, Vallet T, Blanc H, et al. (2019) Host nutritional status affects alphavirus virulence, transmission, and evolution. PLoS Pathog 15(11): e1008089. https://doi.org/10.1371/journal.ppat.1008089

Editor: Richard J. Kuhn, Purdue University, UNITED STATES

Received: June 23, 2019; Accepted: September 17, 2019; Published: November 11, 2019

Copyright: © 2019 Weger-Lucarelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All next-generation sequencing files are uploaded to the small read archive (SRA) under accession number PRJNA573904.

Funding: This work was partially funded by the DARPA program PREventing EMerging Pathogenic Threats (PREEMPT) awarded to MV and JWL. Partial funding was also provided by a faculty start-up package at Virginia Tech awarded to JWL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Competing interests: The authors have declared that no competing interests exist.

Keywords: Arbovirus; Alphavirus; Mosquitoes; Animal models.

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Isolation of #Mayaro Virus from a #Venezuelan Patient with Febrile #Illness, Arthralgias, and #Rash: Further Evidence of Regional Strain Circulation and Possible Long-Term Endemicity (Am J Trop Med Hyg., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Am J Trop Med Hyg. 2019 Oct 7. doi: 10.4269/ajtmh.19-0357. [Epub ahead of print]

Isolation of Mayaro Virus from a Venezuelan Patient with Febrile Illness, Arthralgias, and Rash: Further Evidence of Regional Strain Circulation and Possible Long-Term Endemicity.

Blohm GM1,2,3, Márquez-Colmenarez MC4,1, Lednicky JA2,3, Bonny TS5, Mavian C6,2, Salemi M6,2, Delgado-Noguera L1, Morris JG6,7,2, Paniz-Mondolfi AE8,9,1.

Author information: 1 Venezuelan Science Research Incubator, Zoonoses and Emerging Pathogens Collaborative Network, Barquisimeto, Venezuela. 2 Emerging Pathogens Institute, University of Florida, Gainesville, Florida. 3 Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida. 4 Department of Medicine, Universidad Centroccidental Lisandro Alvarado, Barquisimeto, Venezuela. 5 Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland. 6 Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida. 7 Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida. 8 Laboratory of Cellular Signaling and Parasite Biochemistry, Instituto de Estudios Avanzados (IDEA), Caracas, Venezuela. 9 Instituto Diagnóstico Barquisimeto (IDB), Barquisimeto, Venezuela.

 

Abstract

Fifty-two febrile patients living in Barquisimeto, Venezuela, were screened for arbovirus infection by virus culture during an outbreak of what was thought to be Zika virus infection. We report identification of Mayaro virus (MAYV) on culture of plasma from one patient, an 18-year-old woman with acute febrile illness, arthralgias, and psoriasiform rash. The strain was sequenced and was found to be most closely related to a 1999 strain from French Guiana, which, in turn, was related to two 2014 strains from Haiti. By contrast, previously reported outbreak-related MAYV strains from a sylvatic area 80 miles from where the case patient lived were most closely related to Peruvian isolates. The two strain groups show evidence of having diverged genetically approximately 100 years ago.

PMID: 31595869 DOI: 10.4269/ajtmh.19-0357

Keywords: Mayaro Virus; Venezuela.

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Changing #patterns in the #distribution of the #Mayaro virus #vector #Haemagogus species in #Trinidad, West Indies (Acta Trop., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Acta Trop. 2019 Jul 25:105108. doi: 10.1016/j.actatropica.2019.105108. [Epub ahead of print]

Changing patterns in the distribution of the Mayaro virus vector Haemagogus species in Trinidad, West Indies.

Ali R1, Mohammed A1, Jayaraman J1, Nandram N2, Feng RS1, Lezcano RD2, Seeramsingh R2, Daniel B1, Lovin DD3, Severson DW4, Ramsubhag A5.

Author information: 1 Department of Life Sciences, Faculty of Science & Technology, The University of the West Indies, St. Augustine Campus, Trinidad and Tobago. 2 Insect Vector Control Division, Ministry of Health, Government of Trinidad and Tobago, Trinidad and Tobago. 3 Department of Biological Sciences and Eck institute for Global Health, University of Notre Dame, Notre Dame, Indiana, United States. 4 Department of Life Sciences, Faculty of Science & Technology, The University of the West Indies, St. Augustine Campus, Trinidad and Tobago; Department of Biological Sciences and Eck institute for Global Health, University of Notre Dame, Notre Dame, Indiana, United States. 5 Department of Life Sciences, Faculty of Science & Technology, The University of the West Indies, St. Augustine Campus, Trinidad and Tobago. Electronic address: Adesh.Ramsubhag@sta.uwi.edu.

 

Abstract

The Mayaro virus disease (MAYVD) is an emerging mosquito borne zoonosis that was first reported on the island of Trinidad in 1954. The viral agent for this disease is known to presently be endemic to Central and South America. The enzootic cycle of the Mayaro virus (MAYV) is not fully characterized, though primates are thought to be the main reservoir with Haemagogus species of mosquitoes as the primary vector. This virus has been responsible for several sporadic cases of infections and limited outbreaks, but it is postulated that the MAYVD will become a major epidemic in the future, following in the steps of the recent pandemics caused by Chikungunya and Zika viruses. Mitigating possible major outbreaks of MAYVD in the future would require effective strategies for vector control, for which knowledge on the ecology and distribution of the Haemagogus mosquitoes would be vitally important. In Trinidad, Haemagogus species have only been reported in the northwestern peninsula of the island based on studies up to 1995. However, no recent investigations have been completed to determine the status of this important vector on the island. The aim of this study was to investigate the current spatial distribution of Haemagogus species in the island of Trinidad, West Indies. Adult Haemagogus (Hag.) mosquitoes and larvae were surveyed during a twenty-month period using human bait trapping and ovitraps in major forested areas on the island. Mosquito species were identified using classical taxonomic keys. Haemagogus species were widespread and found in all forest types surveyed. Hag. janthinomys (85.7%) was the most widely distributed and dominant species on the island. Lower levels of Hag. leucocelaneus (7.3%), Hag. equinus (6.4%) and Hag. celeste (0.6%) were also collected. Overall, the proportion of mosquitoes collected in the wet season (June – December) was 3.5 times more than in the dry season (January – May). Mangroves, young secondary forests, semi-evergreen and evergreen forest types had relatively high mean abundance levels of Haemagogus species as compared to deciduous and montane forests. Proximity analysis suggests that population settlements within a 1 km buffer of the forest peripherals may be at risk for any emerging arboviral disease associated with these mosquito vectors. Haemagogus species showed a much wider distribution in Trinidad as compared to previous reports from up to 20 years ago and were prevalent in areas with no known presence of non-human primates. Since the MAYV has been previously implicated in causing infections in vertebrate hosts like rodents, birds and small mammals, the findings of this study suggest that there may be alternative hosts and reservoirs of this virus in the sylvatic cycle in Trinidad, other than primates. This has significant epidemiological implications for mosquito-borne viral infections in the region.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS: Distribution; Haemagogus; Mayaro Virus; Trinidad; Yellow Fever

PMID: 31351893 DOI: 10.1016/j.actatropica.2019.105108

Keywords: Mayaro virus; Mosquitoes; Trinidad.

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Neutralizing #antibodies against #Mayaro virus require Fc effector functions for protective activity (J Exp Med., abstract)

[Source: Journal of Experimental Medicine, full page: (LINK). Abstract, edited.]

Neutralizing antibodies against Mayaro virus require Fc effector functions for protective activity

James T. Earnest, Katherine Basore, Vicky Roy, Adam L. Bailey, David Wang, Galit Alter, Daved H. Fremont, Michael S. Diamond

DOI: 10.1084/jem.20190736 | Published July 23, 201

 

Abstract

Despite causing outbreaks of fever and arthritis in multiple countries, no countermeasures exist against Mayaro virus (MAYV), an emerging mosquito-transmitted alphavirus. We generated 18 neutralizing mAbs against MAYV, 11 of which had “elite” activity that inhibited infection with EC50values of <10 ng/ml. Antibodies with the greatest inhibitory capacity in cell culture mapped to epitopes near the fusion peptide of E1 and in domain B of the E2 glycoproteins. Unexpectedly, many of the elite neutralizing mAbs failed to prevent MAYV infection and disease in vivo. Instead, the most protective mAbs bound viral antigen on the cell surface with high avidity and promoted specific Fc effector functions, including phagocytosis by neutrophils and monocytes. In subclass switching studies, murine IgG2a and humanized IgG1 mAb variants controlled infection better than murine IgG1 and humanized IgG1-N297Q variants. An optimally protective antibody response to MAYV and possibly other alphaviruses may require tandem virus neutralization by the Fab moiety and effector functions of the Fc region.

Submitted: 24 April 2019 – Revision received 11 June 2019 – Accepted: 20 June 2019

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

Keywords: Alphavirus; Mayaro virus; Monoclonal antibodies.

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Infectious #cDNA #clones of two #strains of #Mayaro virus for studies on viral #pathogenesis and #vaccine development (Virology, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virology. 2019 Jul 14;535:227-231. doi: 10.1016/j.virol.2019.07.013. [Epub ahead of print]

Infectious cDNA clones of two strains of Mayaro virus for studies on viral pathogenesis and vaccine development.

Chuong C1, Bates TA1, Weger-Lucarelli J2.

Author information: 1 Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA. 2 Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA, USA. Electronic address: weger@vt.edu.

 

Abstract

Mayaro virus (MAYV; family Togaviridae, genus Alphavirus) is an emerging global threat that can cause severe clinical manifestations similar to Zika, dengue, and chikungunya viruses. Currently, there is a lack of molecular tools to enable a better understanding of the transmission and pathogenesis of MAYV. Here, we detail the development and characterization of infectious clones of two strains of MAYV that produce infectious virus and replicate in mammalian and mosquito cells similarly to wild-type virus. Additionally, clone-derived viruses produced identical infection rates and phenotypes in CD-1 mice compared to the parental strains. This infectious clone system will provide a resource to the research community to analyze MAYV genetic determinants of virulence, determine vector competence, and develop vaccines.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: Alphavirus; Infectious clones; Mayaro virus

PMID: 31325837 DOI: 10.1016/j.virol.2019.07.013

Keywords: Alphavirus; Togavirus; Mayaro virus; Viral pathogenesis.

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#Animal #model of #arthritis and #myositis induced by the #Mayaro virus (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Animal model of arthritis and myositis induced by the Mayaro virus

Franciele Martins Santos, Roberto Sousa Dias, Michelle Dias de Oliveira, Isabella Cristina Toledo Alves Costa, Luciana de Souza Fernandes, Carine Ribeiro Pessoa, Sérgio Luis Pinto da Matta, Vivian Vasconcelos Costa, Danielle G. Souza, Cynthia Canêdo da Silva, Sérgio Oliveira de Paula

Published: May 3, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007375 / This is an uncorrected proof.

 

Abstract

Background

The Mayaro virus (MAYV) is an endemic arbovirus in South American countries, where it is responsible for sporadic outbreaks of Mayaro fever. Clinical manifestations include fever, headache, ocular pain, rash, myalgia, and debilitating and persistent polyarthralgia. Understanding the mechanisms associated with MAYV-induced arthritis is of great importance due to the potential for its emergence, urbanization and dispersion to other regions.

Methods

15-day old Balb/c mice were infected by two distinct pathways, below the forelimb and in the rear footpad. Animals were observed for a period of 21 days. During this time, they were monitored every 24 hours for disease signs, such as weight loss and muscle weakness. Histological damage in the muscles and joints was evaluated 3, 7, 10, 15 and 20 days post-infection. The cytokine profile in serum and muscles during MAYV infection was evaluated by flow cytometry at different post-infection times. For pain analysis, the animals were submitted to the von Frey test and titre in different organs was evaluated throughout the study to obtain viral kinetics.

Findings

Infection by two distinct pathways, below the forelimb and in the rear footpad, resulted in a homogeneous viral spread and the development of acute disease in animals. Clinical signs were observed such as ruffled fur, hunched posture, eye irritation and slight gait alteration. In the physical test, both groups presented loss of resistance, which was associated with histopathological damage, including myositis, arthritis, tenosynovitis and periostitis. The immune response was characterized by a strong inflammatory response mediated by the cytokines TNF-α, IL-6 and INF-γ and chemokine MCP-1, followed by the action of IL-10 and IL-4 cytokines.

Interpretation

The results showed that Balb/c mice represent a promising model to study mechanisms involved in MAYV pathogenesis and for future antiviral testing.

 

Author summary

The Mayaro virus, although restricted to some regions of Latin America, has great potential for emergence, which makes it of great medical-scientific interest. Therefore, pathogenesis study of the MAYV in an animal model has fundamental importance for the determination of viral and host factors that contribute to disease development. In addition, it will allow develop and evaluate the effectiveness of possible antiviral agents. In this study, the authors were able to standardize a disease model for the MAYV in BALB / c mice. From the obtained data it is possible to observe the induction of acute arthritis and myositis, accompanied by the reduction of physical strength of the animals. As described for other alphaviruses in both animal and patient models, the proinflammatory mediators TNF-α, IL-6, INF-γ and MCP-1 were elevated in the serum of MAYV-infected animals and therefore appeared to be mediators which also play an important role in the pathogenesis of MAYV.

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Citation: Santos FM, Dias RS, de Oliveira MD, Costa ICTA, Fernandes LdS, Pessoa CR, et al. (2019) Animal model of arthritis and myositis induced by the Mayaro virus. PLoS Negl Trop Dis 13(5): e0007375. https://doi.org/10.1371/journal.pntd.0007375

Editor: William Klimstra, University of PittsburghUniversity of PittsburghUniversity of PittsburghUniversity of Pittsburgh, UNITED STATES

Received: September 4, 2018; Accepted: April 9, 2019; Published: May 3, 2019

Copyright: © 2019 Santos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The authors are grateful for the financial support of CAPES, CNPq and FAPEMIG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Mayaro virus; Viral pathogenesis; Animal models.

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Protective #immunity by an engineered #DNA #vaccine for #Mayaro virus (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Protective immunity by an engineered DNA vaccine for Mayaro virus

Hyeree Choi, Sagar B. Kudchodkar, Emma L. Reuschel, Kanika Asija, Piyush Borole, Michelle Ho, Krzysztof Wojtak, Charles Reed, Stephanie Ramos, Nathen E. Bopp, Patricia V. Aguilar, Scott C. Weaver, J. Joseph Kim,  [ … ], Kar Muthumani

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Published: February 7, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007042

 

Abstract

Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge.

 

Author summary

Mayaro virus (MAYV) is a mosquito-transmitted virus that causes fever, headache, chills, nausea and joint pain that can last for months after infection. The rising number of cases, due to increased mosquito circulation, and the threat of an epidemic emphasize its importance as an emerging virus, but there are no licensed vaccines to prevent Mayaro infection nor therapeutics to treat it. In this study, we gathered fundamental knowledge on how the immune system responds to MAYV infection, and we evaluated the efficacy of a novel, synthetic DNA envelope vaccine (scMAYV-E) in mice. Analysis of immune responses in mice demonstrated that this vaccine induces potent T cell immunity and antibodies. Mice who receive the vaccine and then are challenged with live MAYV are protected against Mayaro disease. This data provides evidence that the DNA-based MAYV vaccine may be able to prevent Mayaro disease. Thus, the scMAYV-E vaccine is a promising step forward for MAYV vaccine development. Future testing will evaluate whether this vaccine is a viable means to halt the spread of MAYV and protect individuals from Mayaro disease.

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Citation: Choi H, Kudchodkar SB, Reuschel EL, Asija K, Borole P, Ho M, et al. (2019) Protective immunity by an engineered DNA vaccine for Mayaro virus. PLoS Negl Trop Dis 13(2): e0007042. https://doi.org/10.1371/journal.pntd.0007042

Editor: Kenneth E. Olson, Colorado State University, UNITED STATES

Received: April 16, 2018; Accepted: November 30, 2018; Published: February 7, 2019

Copyright: © 2019 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: KM and DBW note funding by Inovio Pharmaceuticals, PA, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: CCR, SR, LH, and JJK are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options. KM discloses grant funding, industry collaborations, speaking honoraria, and fees for consulting. He has received consulting fees from Inovio Pharmaceuticals related to DNA vaccine development. He has a patent application for DNA vaccine development and delivery of DNA encoded monoclonal antibodies pending to Inovio Pharmaceuticals. Remuneration includes direct payments. DBW is the W.W. Smith Charitable Trust Professor in Cancer Research at the Wistar Institute. DBW discloses grant funding, SAB and Board service, industry collaborations, speaking honoraria, and fees for consulting. His service includes serving on scientific review committees and advisory boards. Remuneration includes direct payments and/or stock or stock options. He notes potential conflicts associated with this work with Pfizer, Bristol Myers Squibb, Inovio Pharmaceuticals, Merck, VGXI, Geneos, Astrazeneca and potentially others. Licensing of technology from this laboratory has created over 150 jobs in the biotech/pharma industry. The other authors declare no competing financial interests.

Keywords: Alphavirus; Mayaro virus; Vaccines; Animal models.

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