Macrophages as target cells for Mayaro virus infection: involvement of reactive oxygen species in the inflammatory response during virus replication.
Alphaviruses among the viruses that cause arthritis, consisting in a public health problem worldwide by causing localized outbreaks, as well as large epidemics in humans. Interestingly, while the Old World alphaviruses are arthritogenic, the New World alphaviruses cause encephalitis. One exception is Mayaro virus (MAYV), which circulates exclusively in South America but causes arthralgia and is phylogenetically related to the Old World alphaviruses. Although MAYV-induced arthritis in humans is well documented, the molecular and cellular factors that contribute to its pathogenesis are completely unknown. In this study, we demonstrated for the first time that macrophages, key players in arthritis development, are target cells for MAYV infection, which leads to cell death through apoptosis. We showed that MAYV replication in macrophage induced the expression of TNF, a cytokine that would contribute to pathogenesis of MAYV fever, since TNF promotes an inflammatory profile characteristic of arthritis. We also found a significant increase in the production of reactive oxygen species (ROS) at early times of infection, which coincides with the peak of virus replication and precedes TNF secretion. Treatment of the cells with antioxidant agents just after infection completely abolished TNF secretion, indicating an involvement of ROS in inflammation induced during MAYV infection.
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco E, Sala 18, 21941-902 Rio de Janeiro, RJ Brasil.
Mariana G
MG
Cavalheiro
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco E, Sala 18, 21941-902 Rio de Janeiro, RJ Brasil.
Leandro Silva DA
LS
Costa
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco E, Sala 18, 21941-902 Rio de Janeiro, RJ Brasil.
Holmes S
HS
Campos
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco I, Sala I0-55, 21941-902 Rio de Janeiro, RJ, Brasil.
Letícia S
LS
Alves
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco I, Sala I0-55, 21941-902 Rio de Janeiro, RJ, Brasil.
Iranaia
I
Assunção-Miranda
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco E, Sala 18, 21941-902 Rio de Janeiro, RJ Brasil.
Andrea T DA
AT
Poian
D018354:Alphavirus Infections / Q000150:complications; D001168:Arthritis / Q000821:virology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013020:South America; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014779:Virus Replication
D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha