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A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (1 July 2019) | Viewed by 22519

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Dr. Florine E.M. Scholte

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Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Interests: virus–host interactions; immune activation and evasion; therapeutic interventions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since its re-emergence in 2004, chikungunya virus (CHIKV) has caused several large outbreaks, infecting millions of people. Although CHIKV infection is rarely lethal, the severe and sometimes persistent arthralgia and arthritis it causes pose a significant economic burden on healthcare systems. CHIKV has a broad geographic distribution, potentially putting millions at risk for infection. Due to the expanding geographic spread of competent CHIKV vectors, infected travelers can spark new outbreaks in previously untouched areas. Presently, no licensed vaccines or specific antivirals are available to prevent or combat CHIKV infection. Therefore, developing novel therapeutic interventions should be an important priority. In order to do so, extensive knowledge of the underlying molecular mechanisms of CHIKV infection is required. Despite major discoveries in recent years, there are still important gaps in our understanding of CHIKV replication. These include, but are not limited to, a complete picture of the molecular interactions of CHIKV with both its mosquito and human host, and a detailed understanding of the mechanisms underlying transmission and pathogenesis. Enhanced insight into these dynamics is required to effectively combat the emergence and spread of the virus. In addition, a detailed understanding of the immune responses involved in chronic disease and those required for effective vaccines remain a priority.

This Special Issue will cover a wide range of topics focusing on chikungunya infection and immunity, and aims to help fill the gaps in our current understanding of CHIKV. All types of articles will be considered for publication, including short reports, primary research articles, and reviews.

Dr. Florine E.M. Scholte
Guest Editor

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Keywords

Chikungunya virus
Virus-host interactions
Therapeutic interventions
Virulence factors
Immune activation and evasion
Transmission

Published Papers (5 papers)

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Research

10 pages, 442 KiB

Open AccessArticle

Chikungunya Virus Transmission at Low Temperature by Aedes albopictus Mosquitoes

by B. M. C. Randika Wimalasiri-Yapa, Liesel Stassen, Wenbiao Hu, Laith Yakob, Elizabeth A. McGraw, Alyssa T. Pyke, Cassie C. Jansen, Gregor J. Devine and Francesca D. Frentiu

Pathogens 2019, 8(3), 149; https://doi.org/10.3390/pathogens8030149 - 12 Sep 2019

Cited by 14 | Viewed by 3904

Abstract

Aedes albopictus is an important vector of chikungunya virus (CHIKV). In Australia, Ae. albopictus is currently only known to be present on the islands of the Torres Strait but, should it invade the mainland, it is projected to spread to temperate regions. The ability of Australian Ae. albopictus to transmit CHIKV at the lower temperatures typical of temperate areas has not been assessed. Ae. albopictus mosquitoes were orally challenged with a CHIKV strain from either Asian or East/Central/South African (ECSA) genotypes (10⁷ pfu/mL), and maintained at a constant temperature of either 18 °C or 28 °C. At 3- and 7-days post-infection (dpi), CHIKV RNA copies were quantified in mosquito bodies, and wings and legs using real time polymerase chain reaction (qRT-PCR), while the detection of virus in saliva (a proxy for transmission) was performed by amplification in cell culture followed by observation of cytopathic effect in Vero cells. Of the ≥95% of Ae. albopictus that survived to 7 dpi, all mosquitoes became infected and showed body dissemination of CHIKV at both temperatures and time points. Both the Asian and ECSA CHIKV genotypes were potentially transmissible by Australian Ae. albopictus at 28 °C within 3 days of oral challenge. In contrast, at 18 °C none of the mosquitoes showed evidence of ability to transmit either genotype of CHIKV at 3 dpi. Further, at 18 °C only Ae. albopictus infected with the ECSA genotype showed evidence of virus in saliva at 7 dpi. Overall, infection with the ECSA CHIKV genotype produced higher virus loads in mosquitoes compared to infection with the Asian CHIKV genotype. Our results suggest that lower ambient temperatures may impede transmission of some CHIKV strains by Ae. albopictus at early time points post infection. Full article

(This article belongs to the Special Issue Chikungunya Virus Infections)

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12 pages, 1959 KiB

Open AccessArticle

Whole Transcriptome Analysis of Aedes albopictus Mosquito Head and Thorax Post-Chikungunya Virus Infection

by Ravi kiran Vedururu, Matthew J. Neave, Vinod Sundaramoorthy, Diane Green, Jennifer A. Harper, Paul R. Gorry, Jean-Bernard Duchemin and Prasad N. Paradkar

Pathogens 2019, 8(3), 132; https://doi.org/10.3390/pathogens8030132 - 27 Aug 2019

Cited by 10 | Viewed by 4442

Abstract

Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and causes prolonged arthralgia in patients. After crossing the mosquito midgut barrier, the virus disseminates to tissues including the head and salivary glands. To better understand the interaction between Aedes albopictus and CHIKV, we performed RNASeq analysis on pools of mosquito heads and parts of the thorax 8 days post infection, which identified 159 differentially expressed transcripts in infected mosquitos compared to uninfected controls. After validation using RT-qPCR (reverse transcriptase-quantitative polymerase chain reaction), inhibitor of Bruton’s tyrosine kinase (BTKi), which has previously been shown to be anti-inflammatory in mammals after viral infection, was further evaluated for its functional significance. Knockdown of BTKi using double-stranded RNA in a mosquito cell line showed no significant difference in viral RNA or infectivity titer. However, BTKi gene knocked-down cells showed increased apoptosis 24 hours post-infection compared with control cells, suggesting involvement of BTKi in the mosquito response to viral infection. Since BTK in mammals promotes an inflammatory response and has been shown to be involved in osteoclastogenesis, a hallmark of CHIKV pathogenesis, our results suggest a possible conserved mechanism at play between mosquitoes and mammals. Taken together, these results will add to our understanding of Aedes Albopictus interactions with CHIKV. Full article

(This article belongs to the Special Issue Chikungunya Virus Infections)

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16 pages, 8574 KiB

Open AccessArticle

Targeting the nsp2 Cysteine Protease of Chikungunya Virus Using FDA Approved Library and Selected Cysteine Protease Inhibitors

by Prateek Kumar, Deepak Kumar and Rajanish Giri

Pathogens 2019, 8(3), 128; https://doi.org/10.3390/pathogens8030128 - 15 Aug 2019

Cited by 19 | Viewed by 5338

Abstract

Chikungunya virus (CHIKV) infection is one of the major public health concerns, leading thousands of cases every year in rural as well as urban regions of several countries worldwide, few to mention are India, Philippines, Indonesia, and also in American countries. The structural and non-structural proteins of CHIKV are structurally and functionally similar to other alphaviruses such as Sindbis virus, Venezuelan Equine Encephalitis virus. The precursor protein of non-structural proteins is cleaved by proteolytic activity of non-structural protein (nsp2). This multifunctional nsp2 carry out nucleoside-triphosphatase (NTPase) and RNA helicase activity at its N-terminal and protease activity at C-terminal that makes it primarily a drug target to inhibit CHIKV replication. Until the current date, no suitable treatment for chikungunya infection is available. The introduction of a new drug into the market is a lengthy process, therefore, drug repurposing is now familiar approach that cut off the time and cost of drug discovery. In this study, we have implemented this approach with Food and Drug Administration (FDA) approved drugs and known cysteine protease inhibitors against CHIKV nsp2 protease using structure-based drug discovery. Our extensive docking and molecular dynamics simulations studies leads to two best interacting compounds, Ribostamycin sulfate and E-64, with utmost stable complexes at active site of nsp2 protease. Therefore, these compounds could be suitable for inhibiting CHIKV protease activity, and ultimately the viral replication. Full article

(This article belongs to the Special Issue Chikungunya Virus Infections)

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11 pages, 2360 KiB

Open AccessEditor’s ChoiceArticle

Genetic Characterization of Chikungunya Virus in Field-Caught Aedes aegypti Mosquitoes Collected during the Recent Outbreaks in 2019, Thailand

by Proawpilart Intayot, Atchara Phumee, Rungfar Boonserm, Sriwatapron Sor-suwan, Rome Buathong, Supaporn Wacharapluesadee, Narisa Brownell, Yong Poovorawan and Padet Siriyasatien

Pathogens 2019, 8(3), 121; https://doi.org/10.3390/pathogens8030121 - 2 Aug 2019

Cited by 24 | Viewed by 5029

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne virus belonging to the genus Alphavirus. The virus is transmitted to humans by the bite of infected female Aedes mosquitoes, primarily Aedes aegypti. CHIKV infection is spreading worldwide, and it periodically sparks new outbreaks. There are no specific drugs or effective vaccines against CHIKV. The interruption of pathogen transmission by mosquito control provides the only effective approach to the control of CHIKV infection. Many studies have shown that CHIKV can be transmitted among the Ae. aegypti through vertical transmission. The previous chikungunya fever outbreaks in Thailand during 2008–2009 were caused by CHIKV, the East/Central/South African (ECSA) genotype. Recently, there have been 3794 chikungunya cases in 27 provinces reported by the Bureau of Epidemiology of Health Ministry, Thailand during 1 January–16 June 2019; however, the cause of the re-emergence of CHIKV outbreaks is uncertain. Therefore, the aims of this study were to detect and analyze the genetic diversity of CHIKV infection in field-caught mosquitoes. Both female and male Ae. aegypti were collected from endemic areas of Thailand, and CHIKV detection was done by using E1-nested RT-PCR and sequencing analysis. A total of 1646 Ae. aegypti samples (900 females and 746 males) were tested. CHIKV was detected in 54 (3.28%) and 14 samples (0.85%) in female and male mosquitoes, respectively. Seventeen samples of female Ae. aegypti collected from the Ubon Ratchathani, Chiang Rai, Chiang Mai, Nakhon Sawan, and Songkhla provinces found mutation at E1: A226V. Interestingly, E1: K211E mutation was observed in 50 samples collected from Nong Khai, Bangkok, Prachuap Khiri Khan, and Krabi. In addition, the phylogenetic tree indicated that CHIKV in Ae. aegypti samples were from the Indian Ocean Clade and East/South African Clade. Both clades belong to the ECSA genotype. The information obtained from this study could be used for prediction, epidemiological study, prevention, and effective vector control of CHIKV. For instance, a novel CHIKV strain found in new areas has the potential to lead to a new outbreak. Health authorities could plan and apply control strategies more effectively given the tools provided by this research. Full article

(This article belongs to the Special Issue Chikungunya Virus Infections)

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11 pages, 1427 KiB

Open AccessArticle

Serological Data Shows Low Levels of Chikungunya Exposure in Senegalese Nomadic Pastoralists

by Mame Cheikh Seck, Aida Sadikh Badiane, Julie Thwing, Delynn Moss, Fatou Ba Fall, Jules Francois Gomis, Awa Bineta Deme, Khadim Diongue, Mohamed Sy, Aminata Mbaye, Tolla Ndiaye, Aminata Gaye, Yaye Die Ndiaye, Mamadou Alpha Diallo, Daouda Ndiaye and Eric Rogier

Pathogens 2019, 8(3), 113; https://doi.org/10.3390/pathogens8030113 - 27 Jul 2019

Cited by 10 | Viewed by 3317

Abstract

The chikungunya virus (CHIKV) is spread by Aedes aegypti and Ae. albopictus mosquitos worldwide; infection can lead to disease including joint pain, fever, and rash, with some convalescent persons experiencing chronic symptoms. Historically, CHIKV transmission has occurred in Africa and Asia, but recent outbreaks have taken place in Europe, Indonesia, and the Americas. From September to October 2014, a survey was undertaken with nomadic pastoralists residing in the northeast departments of Senegal. Blood dried on filter paper (dried blood spots; DBS) were collected from 1465 participants of all ages, and assayed for Immunoglobulin G (IgG) antibodies against CHIKV E1 antigen by a bead-based multiplex assay. The overall seroprevalence of all participants to CHIKV E1 was 2.7%, with no persons under 10 years of age found to be antibody positive. Above 10 years of age, clear increases of seroprevalence and IgG levels were observed with increasing age; 7.6% of participants older than 50 years were found to be positive for anti-CHIKV IgG. Reported net ownership, net usage, and gender were all non-significant explanatory variables of seropositivity. These data show a low-level historical exposure of this pastoralist population to CHIKV, with no evidence of recent CHIKV transmission in the past decade. Full article

(This article belongs to the Special Issue Chikungunya Virus Infections)

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