Mimiviruses Interfere With IκBα Degradation

Abstract

Many aspects of giant viruses biology still eludes scientists, with viruses such as Acanthamoeba polyphaga mimivirus (APMV) and Tupanvirus (TPV) possessing large virions covered by fibrils and are cultivated in laboratories using Acanthamoeba cells as hosts. However, little is known about the infectivity of these giant viruses in vertebrate cells. In the present study, we investigated the consequences of the incubation of APMV and Tupanvirus with mammalian cells. These cells express Toll-like receptors (TLR) that are capable of recognizing lipopolysaccharides, favoring the internalization of the antigen and activation of the inflammatory system. By using a lineage of human lung adenocarcinoma cells (A549), we found that APMV and TPV virus particles interact and are internalized by these cells. Furthermore, when treating cells with a fibriless variant of APMV, the M4 strain, there was no significant loss of cell viability, reinforcing the roles of fibrils in cell activation. In addition, we found an upregulation of TLR4 expression and an expected down regulation of IκBα in A549 APMV or TPV-infected cells compared to non-infected cells. Our results suggest that mimiviruses are able to interact with innate immune components such as TLR4, inducing their downstream signaling pathway, which ultimately active proinflammatory responses in lung cells.

Cytopathic effects in Mimivirus infection: understanding the kinetics of virus-cell interaction

“…The authors showed that TPV has a greater cytotoxicity than APMV, generating a greater response through the TLR4 pathway. 37 Based on this knowledge, we hypothesize that TPV appears to be more ‘’toxic’’ after recognition/contact with cells. We hypothesize that this may explain why TPV induces cellular changes prior to APMV and M4, at similar MOIs and at early times of infection.…”

“…Oliveira and collaborators demonstrated that fibrils trigger the TLR4 signaling pathway in lung cells, due to the composition of the fibrils and similarities with LPS. 37 Thus, cells in the presence of fibrils could trigger toxicity responses, while M4, theoretically, would not trigger this signaling pathway. Another work that explored the emergence of mutated strains was done by Mueller and collaborators.…”

“… 45 These data show the diversity of the content carried into the cells, so that such molecules, many without a defined function, can be associated with the modulation of responses even in the absence of replication, as already reported for some mimiviruses. 4 , 37 , 45 We highlight the importance of further studies that seek to understand the composition of the particles of these GVs and the content that is carried into the interior of the host. It is known, for example, that mimiviruses have a range of proteins, RNAs and other molecules that are directed to the cytoplasm by the viral seed and that have different biological functions even in the absence of expression of viral proteins by the cell.…”