Tropism of the Chikungunya Virus

Matusali, Giulia; Colavita, Francesca; Bordi, Licia; Lalle, Eleonora; Ippolito, Giuseppe; Capobianchi, Maria Rosaria; Castilletti, Concetta

doi:10.3390/v11020175

Cited by 98 publications

(106 citation statements)

References 211 publications

(295 reference statements)

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“…In order to validate these findings in a more relevant cell line for human infection, we next investigated the cytotoxic and antiviral potential of tomatidine in Huh7 cells (human hepatic cell line) as hepatocytes are targets during natural CHIKV infection 25 . Furthermore, like with Vero-WHO, these cells are also commonly used in antiviral CHIKV studies 13,[26][27][28] .…”

Section: Resultsmentioning

confidence: 99%

Tomatidine, a natural steroidal alkaloid shows antiviral activity towards chikungunya virus in vitro

Troost

Mulder

Diosa-Toro

et al. 2020

Sci Rep

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in recent decades, chikungunya virus (cHiKV) has re-emerged, leading to outbreaks of chikungunya fever in Africa, Asia and central and South America. the disease is characterized by a rapid onset febrile illness with (poly)arthralgia, myalgia, rashes, headaches and nausea. In 30 to 40% of the cases, CHIKV infection causes persistent (poly)arthralgia, lasting for months or even years after initial infection. Despite the drastic re-emergence and clinical impact there is no vaccine nor antiviral compound available to prevent or control cHiKV infection. Here, we evaluated the antiviral potential of tomatidine towards cHiKV infection. We demonstrate that tomatidine potently inhibits virus particle production of multiple CHIKV strains. Time-of-addition experiments in Huh7 cells revealed that tomatidine acts at a post-entry step of the virus replication cycle. furthermore, a marked decrease in the number of cHiKV-infected cells was seen, suggesting that tomatidine predominantly acts early in infection yet after virus attachment and cell entry. Antiviral activity was still detected at 24 hours post-infection, indicating that tomatidine controls multiple rounds of cHiKV replication. Solasodine and sarsasapogenin, two structural derivatives of tomatidine, also showed strong albeit less potent antiviral activity towards cHiKV. in conclusion, this study identifies tomatidine as a novel compound to combat CHIKV infection in vitro.

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Section: Resultsmentioning

confidence: 99%

Tomatidine, a natural steroidal alkaloid shows antiviral activity towards chikungunya virus in vitro

Troost

Mulder

Diosa-Toro

et al. 2020

Sci Rep

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“…CHIKv infections are not usually associated with congenital abnormalities, although the development of microcephaly after birth in CHIKv-infected neonates has been reported 220,225 . Rare cases of placental and transplacental CHIKv infection have also been reported, and resulted in abortion 226 . alphaviral arthralgia, with such endeavours hopefully leading to new therapeutic approaches.…”

Section: Box 3 | Mother-to-child Infectionsmentioning

confidence: 99%

Rheumatic manifestations of chikungunya: emerging concepts and interventions

Suhrbier

2019

Nat Rev Rheumatol

145

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Chikungunya virus (CHIKV) is a member of a group of globally distributed, mosquito-transmitted arthritogenic alphaviruses that cause sporadic outbreaks of primarily rheumatic disease every 2-50 years 1-4. The largest epidemic of CHIKV disease (hereafter simply referred to as chikungunya) ever recorded began on Lamu Island, Kenya, in 2004 (Fig. 1). The epidemic expanded across four continents, with cases still being reported in 2019 (Fig. 1; Supplementary Table 1). Three major genotypes of CHIKV are now recognized-the Asian, the West African and the Asian and East-Central South African (ECSA) genotypes 5-but a new lineage, the Indian Ocean Lineage (IOL), also emerged from the ECSA genotype during the 2004-2019 epidemic 6. The epidemic reached >100 countries (Supplementary Table 1), caused >10 million cases (Supplementary Table 2), and might arguably be called a pandemic. An estimated 1.3 billion people are at risk of chikungunya 7. Climate change modelling suggests that many more areas of the world (including parts of China, sub-Saharan Africa, South America and the United States) might become able to accommodate transmission of CHIKV in the future 8,9. Chikungunya was previously often viewed as (and for many patients remains) a relatively benign and selflimiting rheumatic disease. However, a considerably more complex spectrum of less common atypical and severe manifestations is now recognized in subgroups of patients, with chikungunya often complicated by comorbidities and co-infections. Hospitalization rates for chikun gunya range from 0.6% to 13% 10-14 and estimates of chikungunya-related mortality range from 0.024% to 0.7% 10,12,15-17. In addition, many patients develop protracted rheumatic disease lasting many months, occasionally years, with a number of sequelae now also recognized 18-22. Estimates for the total economic costs (direct and indirect) of chikungunya have ranged from a median of US$67 for adults and $258 for children in Columbia 23 , to a mean of $150 per outpatient and $3,300 per inpatient in 2006 in Réunion Island 11. In a large study of a chikungunya outbreak in Bangladesh in 2017, >10 days of productivity were lost in ~30% of patients with chikung unya because of severe arthropathy 24. Such costs might be viewed as relatively modest by Western standards; however, the occasionally high attack rate of chikungunya, with up to 30-75% of a given population affected by chikungunya disease at any one time 1,25 , can result in a substantial economic burden, especially in resource-poor communities that are often affected by the disease 26. Considerable research in patients and animal models has now provided extensive insights into the complex Pandemic An epidemic of disease that has spread across a large region; for instance, multiple continents, or even worldwide. Attack rate The total number of new cases of a disease divided by the total population (that is, the percentage of a defined population that is affected by a disease).

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“…Indeed, muscle satellite cells together with fibroblasts, osteoblasts, endothelial cells, and macrophages would be among the cells targeted during acute infection of CHIKV [102,103]. Hussain et al confirmed this model for pathogenesis based on human primary myoblasts [94].…”

Section: Chikungunya Virusmentioning

confidence: 95%

Arboviruses and Muscle Disorders: From Disease to Cell Biology

Filippone

Legros

Jeannin

et al. 2020

Viruses

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Infections due to arboviruses (arthropod-borne viruses) have dramatically increased worldwide during the last few years. In humans, symptoms associated with acute infection of most arboviruses are often described as “dengue-like syndrome”, including fever, rash, conjunctivitis, arthralgia, and muscular symptoms such as myalgia, myositis, or rhabdomyolysis. In some cases, muscular symptoms may persist over months, especially following flavivirus and alphavirus infections. However, in humans the cellular targets of infection in muscle have been rarely identified. Animal models provide insights to elucidate pathological mechanisms through studying viral tropism, viral-induced inflammation, or potential viral persistence in the muscle compartment. The tropism of arboviruses for muscle cells as well as the viral-induced cytopathic effect and cellular alterations can be confirmed in vitro using cellular models. This review describes the link between muscle alterations and arbovirus infection, and the underlying mechanisms.

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Tropism of the Chikungunya Virus

Cited by 98 publications

References 211 publications

Tomatidine, a natural steroidal alkaloid shows antiviral activity towards chikungunya virus in vitro

Tomatidine, a natural steroidal alkaloid shows antiviral activity towards chikungunya virus in vitro

Rheumatic manifestations of chikungunya: emerging concepts and interventions

Arboviruses and Muscle Disorders: From Disease to Cell Biology

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