Epidemic Alphaviruses: Ecology, Emergence and Outbreaks

Azar, Sasha R.; Campos, Rafael K.; Bergren, Nicholas A.; Camargos, Vidyleison Neves; Rossi, Shannan L.

doi:10.3390/microorganisms8081167

Cited by 33 publications

(26 citation statements)

References 302 publications

(615 reference statements)

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“…MAYV causes the disease known as Mayaro fever, which is characterized by nonspecific symptoms, including fever, myalgia, rash, headache, retro-orbital pain, diarrhea, vomiting, lymphadenopathy, leukopenia, and arthralgia [ 15 ]. MAYV is transmitted through the bites of sylvatic mosquitos, mainly members of the Haemagogus genus [ 15 ]. However, several laboratory experiments suggest that urban mosquitos, such as Aedes aegypti or Aedes albopictus , can also spread this virus [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells

Sugasti-Salazar

Llamas-González

Campos

et al. 2021

Viruses

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Mayaro virus (MAYV) hijacks the host’s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPK inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126, or Losmapimod were quantified using plaque assay. Additionally, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

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Section: Introductionmentioning

confidence: 99%

Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells

Sugasti-Salazar

Llamas-González

Campos

et al. 2021

Viruses

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“…CHIKV belongs to the arthritogenic Old World alphaviruses (15,16). CHIKV-infected persons experience a syndrome characterized by fever, rash, arthralgia, and myalgia (reviewed in 17).…”

Section: Introductionmentioning

confidence: 99%

New Insights into Chikungunya Virus Infection and Pathogenesis

et al. 2021

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Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus responsible for major outbreaks of disease since 2004 in the Indian Ocean islands, South east Asia, and the Americas. CHIKV causes debilitating musculoskeletal disorders in humans that are characterized by fever, rash, polyarthralgia, and myalgia. The disease is often self-limiting and nonlethal; however, some patients experience atypical or severe clinical manifestations, as well as a chronic rheumatic syndrome. Unfortunately, no efficient antivirals against CHIKV infection are available so far, highlighting the importance of deepening our knowledge of CHIKV host cell interactions and viral replication strategies. In this review, we discuss recent breakthroughs in the molecular mechanisms that regulate CHIKV infection and lay down the foundations to understand viral pathogenesis. We describe the role of the recently identified host factors co-opted by the virus for infection and pathogenesis, and emphasize the importance of CHIKV nonstructural proteins in both replication complex assembly and host immune response evasion. Expected final online publication date for the Annual Review of Virology, Volume 8 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…MAYV causes the disease known as Mayaro fever, which is characterized by nonspecific symptoms, including fever, myalgia, rash, headache, retro-orbital pain, diarrhea, vomiting, lymphadenopathy, leukopenia and arthralgia [15]. MAYV is transmitted through the bites of sylvatic mosquitos, mainly members of Haemagogus genus [15]. However, several laboratory experiments suggest that urban mosquitos, such as Aedes aegypti or Aedes albopictus, can also spread this virus [16,17].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells

Sugasti¹,

Llamas-González²,

Campos³

et al. 2021

Preprint

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Mayaro virus (MAYV) hijacks the host´s cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPKs inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126 or Losmapimod were quantified using plaque assay. Also, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38β isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38β isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

show abstract

Epidemic Alphaviruses: Ecology, Emergence and Outbreaks

Cited by 33 publications

References 302 publications

Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells

Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells

New Insights into Chikungunya Virus Infection and Pathogenesis

Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells

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