Human metapneumovirus infection in the paediatric population

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Association of cytokine and chemokine gene polymorphisms with severe acute respiratory syndrome

1. The IFN-gamma +874A allele and RANTES -28 G allele are risk factors for SARS susceptibility. 2. The RANTES -28 G allele plays a role in the pathogenesis of SARS. 3. The polymorphisms of IL-10, TNF-alpha, IL-12, IP-10, Mig and MCP-1 are not associated with SARS susceptibility.published_or_final_versio

The macrophage in the pathogenesis of severe acute respiratory syndrome coronavirus infection

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Sialic acid and receptor expression on the respiratory tract in normal subjects and H5N1 and non-avian influenza patients.

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The role of influenza virus gene constellation and viral morphology on cytokine induction, pathogenesis, and viral virulence.

Key Messages 1. H5N1 viruses that cause severe disease in humans are potent inducers of proinflammatory cytokines in contrast to seasonal influenza viruses, and this may play a role in the mechanism of H5N1 pathogenesis. 2. H5N1 viruses are predominantly spherical in morphology. Virus morphology does not influence the ability to induce proinflammatory cytokines. 3. The NS1 viral protein may play a role in the potency of proinflammatory induction. 4. The H5N1 haemagglutinin and neuraminidase do not appear to transfer the high cytokine phenotype. 5. The ability to induce cytokines is a polygenic trait, involving a combination of different viral genes.published_or_final_versio

Pathogenesis of SARS coronavirus infection using human lung epithelial cells: an in vitro model.

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Prevalence of SARS-CoV antibody in all Hong Kong patient contacts.

The near absence of transmission (seroprevalence=0.19%) resulting in asymptomatic infection in this representative high-risk group of close contacts indicates that the prevailing SARS-CoV strains in Hong Kong almost always led to clinically apparent disease.published_or_final_versio

Occult respiratory viral infections in coronial autopsies: a pilot project.

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MERS-CoV at the animal–human interface: inputs on exposure pathways from an expert-opinion elicitation

Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert-opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios, e.g., camels-camels, camels-human, bats/other species to camels/humans, and the role of diverse biological substances (milk, urine, etc.) and potential fomites. Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods) on transmission risk. All experts thought that MERS-CoV-infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated 'most likely' incidence risks of at least 22 and 13% for direct and indirect contact, respectively. The results of our study are consistent with available, yet very limited, published data regarding the potential pathways of transmission of MERS-CoV at the animal-human interface. These results identify key knowledge gaps and highlight the need for more comprehensive, yet focused research to be conducted to better understand transmission between dromedaries and humans.published_or_final_versio

Interferon dysregulation and virus-induced cell death in avian influenza H5N1 virus infections.

1. Hyper-induction of cytokines and chemokines was found in human blood macrophages infected with the avian influenza H5N1 and H9N2/G1 viruses, as compared to those infected with human influenza H1N1 virus. 2. IRF3 played a significant role in the hyperinduction of cytokines including IFN-β, IFN-λ1,IFN-α subtypes, MCP-1, and TNF-α, and also played a part in subsequent cytokine-induced cell signalling cascades. 3. Compared with H1N1 viruses, avian influenza viruses including H5N1/97 and its precursors triggered a caspase-mediated but delayed apoptotic response in human macrophages. 4. Therapies that can minimise immunopathology-associated dysregulation of innate immunity without impairing effective host defence may be valuable adjuncts to antiviral therapy.published_or_final_versio