Lower temperatures reduce type I interferon activity and promote alphaviral arthritis

Prow, Natalie A.; Tang, Bing; Gardner, Joy; Le, Thuy T.; Taylor, Adam; Poo, Yee Suan; Nakayama, Eri; Hirata, Thiago Dominguez Crespo; Nakaya, Helder I.; Slonchak, Andrii; Mukhopadhyay, Pamela; Mahalingam, Suresh; Schroder, Wayne A.; Klimstra, William B.; Suhrbier, Andreas

doi:10.1371/journal.ppat.1006788

Cited by 41 publications

(54 citation statements)

References 109 publications

(178 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The fever is often of rapid onset and high grade, with one large study reporting a mean maximum body temperature of 39.8 °C (SD ±0.5 °C) and fever duration of 4.88 days (SD ±2.7 days) 24 . Polyarthralgia usually starts around the same time as the fever and is often incapacitating, usually symmetrical and primarily involves peripheral joints 19,24,35,36 (Fig. 2).…”

Section: Acute Chikungunyamentioning

confidence: 99%

“…The anti-alphaviral activity of type I interferons is optimal at 37 °C and this activity decreases with decreasing temperatures, being noticeably lower even with a reduction of only 2 °C (reF. 36 ).…”

Section: Antiviral Versus Arthritic Responsesmentioning

confidence: 99%

“…However, in addition to inhibiting viral replication, type I interferons can also promote arthritis. For example, injection of polyinosinic:polycytidylic acid (a mimic of viral double-strand RNA and potent inducer of type I interferon production) into the feet of mice can induce arthritis, and recapitulates much of the inflammatory gene expression signature that occurs in mouse feet during CHIKV arthropathy 36 .…”

Section: Antiviral Versus Arthritic Responsesmentioning

confidence: 99%

See 2 more Smart Citations

Rheumatic manifestations of chikungunya: emerging concepts and interventions

2019

Self Cite

View full text Add to dashboard Cite

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).

show abstract

Section: Acute Chikungunyamentioning

confidence: 99%

Section: Antiviral Versus Arthritic Responsesmentioning

confidence: 99%

Section: Antiviral Versus Arthritic Responsesmentioning

confidence: 99%

See 1 more Smart Citation

Rheumatic manifestations of chikungunya: emerging concepts and interventions

2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…This phenotype was confirmed to be independent of any potential thermal instability of the virus particles. In addition, recent reports have revealed that the antiviral effects of IFN-I and RNAse L responses could be significantly lower at cooler temperatures than in warmer environments [21][22][23][24]. However, BgV still did not replicate at 37˚C in cell lines deficient in IFN-I responses (Vero [25,26] and MEF IFNAR-/-) or RNAse L (MEF RNL-/-), indicating that BgV host-restriction was not only due to IFN-I-or RNAse L-dependent mechanisms.…”

Section: Fig 6 Microphotographs Of Meningo-encephalitis In the Brainmentioning

confidence: 99%

NS4/5 mutations enhance flavivirus Bamaga virus infectivity and pathogenicity in vitro and in vivo

et al. 2020

View full text Add to dashboard Cite

Flaviviruses such as yellow fever, dengue or Zika viruses are responsible for significant human and veterinary diseases worldwide. These viruses contain an RNA genome, prone to mutations, which enhances their potential to emerge as pathogens. Bamaga virus (BgV) is a mosquito-borne flavivirus in the yellow fever virus group that we have previously shown to be host-restricted in vertebrates and horizontally transmissible by Culex mosquitoes. Here, we aimed to characterise BgV host-restriction and to investigate the mechanisms involved. We showed that BgV could not replicate in a wide range of vertebrate cell lines and animal species. We determined that the mechanisms involved in BgV host-restriction were independent of the type-1 interferon response and RNAse L activity. Using a BgV infectious clone and two chimeric viruses generated as hybrids between BgV and West Nile virus, we demonstrated that BgV host-restriction occurred post-cell entry. Notably, BgV host-restriction was shown to be temperature-dependent, as BgV replicated in all vertebrate cell lines at 34˚C but only in a subset at 37˚C. Serial passaging of BgV in Vero cells resulted in adaptive mutants capable of efficient replication at 37˚C. The identified mutations resulted in amino acid substitutions in NS4A-S124F, NS4B-N244K and NS5-G2C, all occurring close to a viral protease cleavage site (NS4A/2K and NS4B/NS5). These mutations were reverse engineered into infectious clones of BgV, which revealed that NS4B-N244K and NS5-G2C were sufficient to restore BgV replication in vertebrate cells at 37˚C, while NS4A-S124F further increased replication efficiency. When these mutant viruses were injected into immunocompetent mice, alongside BgV and West Nile virus chimeras, infection and neurovirulence were enhanced as determined by clinical scores, seroconversion, microneutralisation, viremia, histopathology and immunohistochemistry, confirming the involvement of these residues in the attenuation of BgV. Our studies identify a new mechanism of host-restriction and attenuation of a mosquito-borne flavivirus.

show abstract

“…Another intriguing question, which was not addressed in this epidemiologic study, is why chikungunya virus tends to preferentially infect distal joints. Notably, a recent study by Prow et al showed that mice infected with chikungunya virus have more severe disease, more robust viral replication, and impaired antiviral type I interferon (IFN) response when the mice are housed at lower temperatures . Since distal joints are slightly cooler than proximal joints, temperature‐dependent antiviral immunity could be a possible explanation of why chikungunya virus preferentially affects small joints in the distal extremities .…”

mentioning

confidence: 99%