Matrix metalloproteinases (MMPs) are involved in extracellular matrix remodeling through the degradation of extracellular matrix components and are also involved in the inflammatory response by regulating the pro-inflammatory cytokines TNF-α and IL-1β. Dysregulation in the inflammatory response and changes in the extracellular matrix by MMPs are related to the development of various diseases including lung and cardiovascular diseases. Therefore, numerous studies have been conducted to understand the role of MMPs in disease pathogenesis. MMPs are involved in the pathogenesis of infectious diseases through a dysregulation of the activity and expression of MMPs. In this review, we discuss the role of MMPs in infectious diseases and inflammatory responses. Furthermore, we present the potential of MMPs as therapeutic targets in infectious diseases.

Background: Influenza virus infection triggers acute cardiovascular events. Several studies have demonstrated that influenza A virus infection was associated with immune cell influx and increased production of inflammatory cytokines in the atherosclerotic plaque lesion, but the underlying mechanism for these findings is not clear. Methods: We examined the expression levels of matrix metalloproteinases (MMPs) by influenza A virus infection in human cells using quantitative real-time polymerase chain reaction, Western blot, and human MMP-13 enzyme-linked immunosorbent assay. In an animal study, protein expression in the plaque lesions of apolipoprotein E (ApoE)-deficient mice were analyzed by immunohistochemistry and Western blot. Results: We confirmed that MMP-13 was increased in influenza A virus-infected cells. In the aorta of infected ApoE-deficient mice, MMP-13 was increased at 3 days after infection. Immunohistochemical staining results suggested that collagen was degraded in the MMP-13 expression area and that macrophages were the main source of MMP-13 expression. Furthermore, the expression of MMP-13 was regulated by influenza A virus through activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Conclusions: In this study, we demonstrated that p38 MAPK-mediated MMP-13 expression by influenza A virus infection led to destabilization of vulnerable atherosclerotic plaques in the artery.

This study investigated the drug repositioning potential of metformin for cardiovascular risk due to influenza A virus infection. Statistical analysis was performed to analyze factors related to the risk of death after IAV infection in diabetic patients. Through in vitro and in vivo experiments, the effect of metformin on influenza A virus infection in non-diabetic conditions was analyzed. In logistic regression analysis, influenza vaccination (OR = 0.378, p-value = 0.007, 0.186 < 95% C·I < 0.768) and metformin treatment (OR = 0.380, p-value = 0.016, 0.173 < 95% C·I < 0.835) were associated with a decreased influenza-related mortality in diabetic patients. In vitro and in vivo studies showed that viral replication and influenza A virus-induced cytokine expression were inhibited by metformin. In particular, MCP-1 and IP-10, cytokines related to cell infiltration and cardiovascular disease development, were significantly reduced by metformin under influenza A virus infection condition. As a result, the acute exacerbation of atherosclerosis caused by influenza A virus in mouse aorta was inhibited by metformin. In addition, we found that regulation of AKT/MAPK signaling plays an important role in the mechanism of metformin. In conclusion, we demonstrated the potential and mechanism of metformin as a treatment for acute exacerbation of atherosclerosis caused by influenza A virus infection.

Face masks are used to protect the wearer from harmful external air and to prevent transmission of viruses from air exhaled by potentially infected wearers to the surrounding people. In this study, we examined the potential utility of masks for collecting viruses contained in exhaled breath and detected the collected viruses via various molecular tests. Using KF94 masks, the inner electrostatic filter was selected for virus collection, and an RNA extraction protocol was developed for the face mask. Virus detection in worn mask samples was performed using PCR and rolling circle amplification (RCA) tests and four different target genes (N, E, RdRp, and ORF1ab genes). The present study confirmed that the mask sample tests showed positive SARS-CoV-2 results, similar to the PCR tests using nasopharyngeal swab samples. In addition, the quantity of nucleic acid collected in the masks linearly increased with wearing time. These results suggest that samples for SARS-CoV-2 tests can be collected in a noninvasive, quick, and easy method by simply submitting worn masks from subjects, which can significantly reduce the hassle of waiting at airports or public places and concerns about cross-infection. In addition, it is expected that miniaturization technology will integrate PCR assays on face masks in the near future, and mask-based self-diagnosis would play a significant role in resolving the pandemic situation.

Background: The influenza virus is reportedly associated with 3‐5 million cases of severe illness and 250 000‐500 000 deaths annually worldwide.Objectives: We investigated the variation of influenza A virus in Korea and examined the association with death.Methods: A total of 13 620 cases were enrolled in the Hospital‐based Influenza Morbidity & Mortality surveillance system in Korea during 2011‐2016. Among these cases, a total of 4725 were diagnosed with influenza using RT‐PCR (influenza A; n = 3696, influenza B; n = 928, co‐infection; n = 101). We used 254 viral sequences from the 3696 influenza A cases for phylogenetic analysis using the BioEdit and MEGA 6.06 programs.Results: We found that the sequences of A/H3N2 in the 2011‐2012 season belong to subgroup 3C.1, whereas the sequences in the 2012‐2013 season pertain to subgroup 3C.2. The sequences in the 2013‐2014 and 2014‐2015 seasons involve subgroups 3C.3a and 3C.2a. The A/H1N1pdm09 subtype belongs to subgroup 6 and contains two clusters. In addition, sequence analysis confirmed the several substitutions of internal genes and gene substitutions associated with drug resistance (I222V in NA and S31N in M2) in the fatal cases. While statistical analysis found no significant associations between genetic differences in the viruses and mortality, mortality was associated with certain host factors, such as chronic lung disease.Conclusions: In conclusion, influenza A virus clade changes occurred in Korea during the 2011‐2016 seasons. These data, along with antigenic analysis, can aid in selecting effective vaccine strains. We confirmed that fatality in influenza A cases was related to underlying patient diseases, such as chronic lung disease, and further studies are needed to confirm associations between mortality and viral genetic substitutions.