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Suppression of chikungunya virus replication and differential innate responses of human peripheral blood mononuclear cells during co-infection with dengue virus.

ABSTRACT: Dengue and chikungunya are viral diseases transmitted to humans by infected Aedes spp. mosquitoes. With an estimated 390 million infected people per year dengue virus (DENV) currently causes the most prevalent arboviral disease. During the last decade chikungunya virus (CHIKV) has caused large outbreaks and has expanded its territory causing millions of cases in Asia, Africa and America. The viruses share a common mosquito vector and during the acute phase cause similar flu-like symptoms that can proceed to more severe or debilitating symptoms. The growing overlap in the geographical distribution of these mosquito-borne infections has led to an upsurge in reported cases of DENV/CHIKV co-infections. Unfortunately, at present we have little understanding of consequences of the co-infections to the human host. The overall aim of this study was to define viral replication dynamics and the innate immune signature involved in concurrent DENV and CHIKV infections in human peripheral blood mononuclear cells (PBMCs). We demonstrate that concomitant infection resulted in a significant reduction of CHIKV progeny and moderate enhancement of DENV production. Remarkably, the inhibitory effect of DENV on CHIKV infection occurred independently of DENV replication. Furthermore, changes in type I IFN, IL-6, IL-8, TNF-?, MCP-1 and IP-10 production were observed during concomitant infections. Notably, co-infections led to a significant increase in the levels of TNF-? and IL-6, cytokines that are widely considered to play a crucial role in the early pathogenesis of both viral diseases. In conclusion, our study reveals the interplay of DENV/CHIKV during concomitant infection and provides a framework to investigate viral interaction during co-infections.

SUBMITTER: Ruiz Silva M

PROVIDER: S-EPMC5500378 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Suppression of chikungunya virus replication and differential innate responses of human peripheral blood mononuclear cells during co-infection with dengue virus.

Ruiz Silva Mariana M Aguilar Briseño José A JA Upasani Vinit V van der Ende-Metselaar Heidi H Smit Jolanda M JM Rodenhuis-Zybert Izabela A IA

PLoS neglected tropical diseases 20170623 6

Dengue and chikungunya are viral diseases transmitted to humans by infected Aedes spp. mosquitoes. With an estimated 390 million infected people per year dengue virus (DENV) currently causes the most prevalent arboviral disease. During the last decade chikungunya virus (CHIKV) has caused large outbreaks and has expanded its territory causing millions of cases in Asia, Africa and America. The viruses share a common mosquito vector and during the acute phase cause similar flu-like symptoms that ca ...[more]

PMID: 28644900

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Project description:Background & objectivesThere are reports about the susceptibility of Aedes mosquitoes to ZIKV from various countries, however, no such information is available from Indian sub-continent, although, high level of group cross-reactivity of ZIKV with other flaviviruses has been reported. During outbreak situations, many cases of Dengue (DEN) and Chikungunya (CHIK) are reported. In such scenario, vector mosquitoes are likely to get co-infection/secondary-infection with one or other virus. The present study was carried out to determine the susceptibility of Indian strain of Aedes aegypti to Zika virus (ZIKV) strain (MR-766) and the effect of co-infection/super-infection with either dengue virus (serotype-2) (DENV) or chikungunya virus (CHIKV) on ZIKV replication.MethodsAe. aegypti mosquitoes used in this study were reared for many generations since 1980 at laboratory colony maintained at the ICMR-National Institute of Virology, Pune, India. Transmissibility of ZIKV from infected mosquitoes to suckling mice was also studied. Mosquitoes were experimentally infected with ZIKV and super-infected with either DENV or CHIKV via membrane-feeding route and incubated for 14 days at 28±2°C and humidity of 85±5 per cent. Replication of these viruses in mosquitoes was confirmed using real-time reverse transcription-polymerase chain reaction and immunofluorescence assay. Twenty infected mosquitoes were allowed to feed upon four suckling CD1 mice for about 30 min. Transmission of the ZIKV by infected mosquitoes to suckling mice was confirmed by the appearance of clinical signs and the presence of viral RNA in different organs.ResultsConcomitant infection of mosquitoes with all the three viruses showed simultaneous propagation of all three viruses, confirmed by real time RT-PCR and IFA. Infection of mosquitoes with CHIKV followed by ZIKV showed positivity in individual head squashes (7%) for both viruses using IFA; only 8.3 per cent showed dual positivity with primary infection of ZIKV followed by DENV; 8.3 per cent dual infection positivity was observed when infected with DENV followed by ZIKV; 5 per cent showed dual infection was observed when infected with ZIKV followed by CHIKV. Ae. aegypti was found to be susceptible to ZIKV strain as ZIKV could be detected from the second post-infection day (PID) in infected mosquitoes. Transmission of ZIKV to mice by the bite of infected Ae. aegypti establishes this species as a potential vector.Interpretation & conclusionsFrom super-infection experiments, it was concluded that ZIKV might have a relative advantage in replication dynamics over DENV. Vertical transmission was not observed for ZIKV in experimentally infected mosquitoes (n=920 larvae). Further studies are required to understand the possibility of silently circulating ZIKV in India, which remain non-detected because of lack of surveillance.

Project description:Dengue viruses are the most important arboviral pathogens in the world, which have adapted to human transmission and replication over several hundred years and were initially recognized to cause outbreaks of clinical disease in tropical and subtropical countries by Aedes aegypti mosquitoes. Subsequent global expansion of dengue infection outbreaks has occurred, with millions of cases yearly, probably from a combination of factors including proliferation of international travel and trade, possibly global climate changes, adaptation of the vectors to new environment, and emergence of a new mosquito vector, Aedes albopictus. Chikungunya virus, also transmitted by Aedes mosquitoes, causes a very similar clinical disease but with more prominent arthralgia or arthritis and was originally described in Africa in the 1960s. After a quiescent period of several decades, it reemerged in Africa in 2004 and rapidly spread across the Indian Ocean to involve Asian countries and parts of Europe. However, the past 2 years have seen the emergence of chikungunya virus in the western hemisphere with major outbreaks in the Caribbean and the Americas. Similar to dengue virus, chikungunya virus has adapted to Ae. albopictus mosquitoes which can transmit the disease. Although dengue infection is a more deadly disease especially in young children, chikungunya infection can cause prolonged severe disability and occasionally rare fatalities from encephalitis. No specific treatment is available for either diseases, but development of an effective vaccine for dengue infection is in progress. Until 2007, Zika virus [also transmitted by Aedes species] was associated with only sporadic mild infections in Africa and Asia. In 2007, Zika virus for the first time caused an outbreak beyond Africa and Asia to the Yap Island in the Federated States of Micronesia. Since then Zika virus has spread to French Polynesia, New Caledonia, Cook Islands, and Easter Island in the southeastern Pacific Ocean [Chile] in 2014 and by 2015 to Brazil. By January 2016, it became evident that Zika virus had caused an explosive outbreak in the Americas and the Caribbean with over 30 countries affected. On February 1, 2016, the World Health Organization declared Zika outbreak a global public health emergency. Zika virus infection is most commonly asymptomatic, and 20% of patients may develop a mild viral disease, but of major concern is the reported association of microcephaly in infected pregnant women in Brazil. This chapter explores the history, epidemiology, pathogenesis, clinical features, treatment, and prevention of these rapidly emerging zoonoses.

Dataset Information

Suppression of chikungunya virus replication and differential innate responses of human peripheral blood mononuclear cells during co-infection with dengue virus.

Publications

Suppression of chikungunya virus replication and differential innate responses of human peripheral blood mononuclear cells during co-infection with dengue virus.

Similar Datasets

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