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1.
Cell Mol Life Sci ; 78(21-22): 6735-6744, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1377320

ABSTRACT

Kallikrein-related peptidases (KLKs) or kallikreins have been linked to diverse (patho) physiological processes, such as the epidermal desquamation and inflammation, seminal clot liquefaction, neurodegeneration, and cancer. Recent mounting evidence suggests that KLKs also represent important regulators of viral infections. It is well-established that certain enveloped viruses, including influenza and coronaviruses, require proteolytic processing of their hemagglutinin or spike proteins, respectively, to infect host cells. Similarly, the capsid protein of the non-enveloped papillomavirus L1 should be proteolytically cleaved for viral uncoating. Consequently, extracellular or membrane-bound proteases of the host cells are instrumental for viral infections and represent potential targets for drug development. Here, we summarize how extracellular proteolysis mediated by the kallikreins is implicated in the process of influenza (and potentially coronavirus and papillomavirus) entry into host cells. Besides direct proteolytic activation of viruses, KLK5 and 12 promote viral entry indirectly through proteolytic cascade events, like the activation of thrombolytic enzymes that also can process hemagglutinin, while additional functions of KLKs in infection cannot be excluded. In the light of recent evidence, KLKs represent potential host targets for the development of new antivirals. Humanized animal models to validate their key functions in viral infections will be valuable.


Subject(s)
COVID-19/enzymology , COVID-19/virology , Host Microbial Interactions/physiology , Kallikreins/metabolism , SARS-CoV-2 , Virus Diseases/enzymology , Animals , Asthma/etiology , Coronavirus/genetics , Coronavirus/pathogenicity , Coronavirus/physiology , Host Microbial Interactions/genetics , Humans , Orthomyxoviridae/genetics , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Papillomavirus Infections/enzymology , Papillomavirus Infections/virology , Picornaviridae Infections/complications , Picornaviridae Infections/enzymology , Picornaviridae Infections/virology , Protein Processing, Post-Translational , Proteolysis , Rhinovirus/pathogenicity , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Varicella Zoster Virus Infection/enzymology , Varicella Zoster Virus Infection/virology , Viral Proteins/genetics , Viral Proteins/metabolism , Virus Diseases/virology , Virus Internalization
2.
Epidemiol Infect ; 149: e96, 2021 04 14.
Article in English | MEDLINE | ID: covidwho-1182771

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and Middle East respiratory syndrome coronavirus. We examined laboratory animal and human studies. The literature on infective dose, transmission and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severe symptoms. Higher viral load measures did not reflect coronavirus disease 2019 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Our review suggests that it is small, perhaps about 100 particles. Further work is also required on the relationship between routes of transmission, infective dose, co-infection and outcomes.


Subject(s)
COVID-19/transmission , SARS-CoV-2/pathogenicity , Viral Load , Adenoviridae/pathogenicity , Animals , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Chlorocebus aethiops , Communicable Disease Control , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Cricetinae , Enterovirus/pathogenicity , Ferrets , Humans , Macaca mulatta , Mice , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Orthomyxoviridae/pathogenicity , Respiratory Syncytial Viruses/pathogenicity , Rhinovirus/pathogenicity , SARS Virus/pathogenicity , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , Severe Acute Respiratory Syndrome/virology , Virus Diseases/epidemiology , Virus Diseases/transmission , Virus Diseases/virology
4.
J Med Virol ; 92(11): 2623-2630, 2020 11.
Article in English | MEDLINE | ID: covidwho-935126

ABSTRACT

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread around the world, causing serious illness and death and creating a heavy burden on the healthcare systems of many countries. Since the virus first emerged in late November 2019, its spread has coincided with peak circulation of several seasonal respiratory viruses, yet some studies have noted limited coinfections between SARS-CoV-2 and other viruses. We use a mathematical model of viral coinfection to study SARS-CoV-2 coinfections, finding that SARS-CoV-2 replication is easily suppressed by many common respiratory viruses. According to our model, this suppression is because SARS-CoV-2 has a lower growth rate (1.8/d) than the other viruses examined in this study. The suppression of SARS-CoV-2 by other pathogens could have implications for the timing and severity of a second wave.


Subject(s)
COVID-19/virology , Coinfection/virology , Common Cold/epidemiology , Influenza, Human/epidemiology , Models, Theoretical , COVID-19/epidemiology , Coinfection/epidemiology , Common Cold/virology , Humans , Influenza, Human/virology , Respiratory Syncytial Viruses/pathogenicity , Rhinovirus/pathogenicity , SARS-CoV-2/pathogenicity
5.
J Allergy Clin Immunol Pract ; 8(2): 588-595.e4, 2020 02.
Article in English | MEDLINE | ID: covidwho-822716

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV)- and rhinovirus (RV)-induced bronchiolitis are associated with an increased risk of asthma, but more detailed information is needed on virus types. OBJECTIVE: To study whether RSV or RV types are differentially associated with the future use of asthma control medication. METHODS: Over 2 consecutive winter seasons (2008-2010), we enrolled 408 children hospitalized for bronchiolitis at age less than 24 months into a prospective, 3-center, 4-year follow-up study in Finland. Virus detection was performed by real-time reverse transcription PCR from nasal wash samples. Four years later, we examined current use of asthma control medication. RESULTS: A total of 349 (86%) children completed the 4-year follow-up. At study entry, the median age was 7.5 months, and 42% had RSV, 29% RV, 2% both RSV and RV, and 27% non-RSV/-RV etiology. The children with RV-A (adjusted hazard ratio, 2.3; P = .01), RV-C (adjusted hazard ratio, 3.5; P < .001), and non-RSV/-RV (adjusted hazard ratio, 2.0; P = .004) bronchiolitis started the asthma control medication earlier than did children with RSV bronchiolitis. Four years later, 27% of patients used asthma control medication; both RV-A (adjusted odds ratio, 3.0; P = .03) and RV-C (adjusted odds ratio, 3.7; P < .001) etiology were associated with the current use of asthma medication. The highest risk was found among patients with RV-C, atopic dermatitis, and fever (adjusted odds ratio, 5.0; P = .03). CONCLUSIONS: Severe bronchiolitis caused by RV-A and RV-C was associated with earlier initiation and prolonged use of asthma control medication. The risk was especially high when bronchiolitis was associated with RV-C, atopic dermatitis, and fever.


Subject(s)
Asthma , Bronchiolitis , Influenza A Virus, H1N1 Subtype , Picornaviridae Infections , Rhinovirus , Asthma/drug therapy , Asthma/epidemiology , Asthma/virology , Bronchiolitis/drug therapy , Bronchiolitis/epidemiology , Child , Child, Preschool , Finland/epidemiology , Follow-Up Studies , Humans , Infant , Male , Picornaviridae Infections/complications , Prospective Studies , Respiratory Sounds , Rhinovirus/classification , Rhinovirus/pathogenicity
7.
Annu Rev Virol ; 7(1): 83-101, 2020 09 29.
Article in English | MEDLINE | ID: covidwho-35145

ABSTRACT

The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field.


Subject(s)
Coronavirus Infections/epidemiology , Influenza, Human/epidemiology , Pandemics , Picornaviridae Infections/epidemiology , Pneumonia, Viral/epidemiology , Respiratory Tract Infections/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/transmission , Coronavirus Infections/virology , Humans , Humidity , Infectious Disease Incubation Period , Influenza, Human/transmission , Influenza, Human/virology , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Picornaviridae Infections/transmission , Picornaviridae Infections/virology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Respiratory Tract Infections/transmission , Respiratory Tract Infections/virology , Rhinovirus/pathogenicity , Rhinovirus/physiology , SARS Virus/pathogenicity , SARS Virus/physiology , SARS-CoV-2 , Seasons , Severe Acute Respiratory Syndrome/transmission , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Temperature
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