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1.
PLoS Pathog ; 17(7): e1009381, 2021 07.
Article in English | MEDLINE | ID: covidwho-1291654

ABSTRACT

Clearance of viral infections, such as SARS-CoV-2 and influenza A virus (IAV), must be fine-tuned to eliminate the pathogen without causing immunopathology. As such, an aggressive initial innate immune response favors the host in contrast to a detrimental prolonged inflammation. The complement pathway bridges innate and adaptive immune system and contributes to the response by directly clearing pathogens or infected cells, as well as recruiting proinflammatory immune cells and regulating inflammation. However, the impact of modulating complement activation in viral infections is still unclear. In this work, we targeted the complement decay-accelerating factor (DAF/CD55), a surface protein that protects cells from non-specific complement attack, and analyzed its role in IAV infections. We found that DAF modulates IAV infection in vivo, via an interplay with the antigenic viral proteins hemagglutinin (HA) and neuraminidase (NA), in a strain specific manner. Our results reveal that, contrary to what could be expected, DAF potentiates complement activation, increasing the recruitment of neutrophils, monocytes and T cells. We also show that viral NA acts on the heavily sialylated DAF and propose that the NA-dependent DAF removal of sialic acids exacerbates complement activation, leading to lung immunopathology. Remarkably, this mechanism has no impact on viral loads, but rather on the host resilience to infection, and may have direct implications in zoonotic influenza transmissions.


Subject(s)
CD55 Antigens/physiology , Influenza A Virus, H1N1 Subtype/isolation & purification , Lung/immunology , Viremia/immunology , Animals , Bronchoalveolar Lavage Fluid/immunology , CD55 Antigens/chemistry , CD55 Antigens/deficiency , Chemotaxis, Leukocyte , Complement Activation , Hemagglutinin Glycoproteins, Influenza Virus/physiology , Host Adaptation , Host Specificity , Host-Pathogen Interactions , Influenza A Virus, H1N1 Subtype/enzymology , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza A Virus, H1N1 Subtype/physiology , Interferon-gamma/analysis , Lung/pathology , Lung/virology , Mice , Mice, Inbred C57BL , N-Acetylneuraminic Acid , Neuraminidase/physiology , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/pathology , Viral Load , Viral Proteins/physiology , Virulence , Virus Replication , Weight Loss
2.
Biosensors (Basel) ; 11(1)2020 Dec 31.
Article in English | MEDLINE | ID: covidwho-1006988

ABSTRACT

The United States Centers for Disease Control and Prevention considers saliva contact the lead transmission means of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). Saliva droplets or aerosols expelled by heavy breathing, talking, sneezing, and coughing may carry this virus. People in close distance may be exposed directly or indirectly to these droplets, especially those droplets that fall on surrounding surfaces and people may end up contracting COVID-19 after touching the mucosa tissue on their faces. It is of great interest to quickly and effectively detect the presence of SARS-CoV-2 in an environment, but the existing methods only work in laboratory settings, to the best of our knowledge. However, it may be possible to detect the presence of saliva in the environment and proceed with prevention measures. However, detecting saliva itself has not been documented in the literature. On the other hand, many sensors that detect different organic components in saliva to monitor a person's health and diagnose different diseases that range from diabetes to dental health have been proposed and they may be used to detect the presence of saliva. This paper surveys sensors that detect organic and inorganic components of human saliva. Humidity sensors are also considered in the detection of saliva because a large portion of saliva is water. Moreover, sensors that detect infectious viruses are also included as they may also be embedded into saliva sensors for a confirmation of the virus' presence. A classification of sensors by their working principle and the substance they detect is presented. This comparison lists their specifications, sample size, and sensitivity. Indications of which sensors are portable and suitable for field application are presented. This paper also discusses future research and challenges that must be resolved to realize practical saliva sensors. Such sensors may help minimize the spread of not only COVID-19 but also other infectious diseases.


Subject(s)
Biological Monitoring/instrumentation , COVID-19/prevention & control , SARS-CoV-2/isolation & purification , Saliva/chemistry , Saliva/virology , Biological Monitoring/methods , COVID-19/enzymology , COVID-19/etiology , COVID-19/immunology , Communicable Diseases/enzymology , Communicable Diseases/etiology , Communicable Diseases/immunology , Communicable Diseases/virology , Humans , Influenza A Virus, H1N1 Subtype/chemistry , Influenza A Virus, H1N1 Subtype/enzymology , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H1N1 Subtype/isolation & purification , SARS-CoV-2/chemistry , SARS-CoV-2/immunology , Saliva/enzymology , Saliva/immunology , Viruses/chemistry , Viruses/enzymology , Viruses/immunology , Viruses/isolation & purification
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