A Critical Role of Cell Tropism for the Pathogenesis of Influenza

Influenza A virus, together with Influenza B virus, Influenza C virus, Isavirus and Thogotovirus, are the five genera forming the family Orthomyxoviridae. Orthomyxoviridae are enveloped, negative-stranded RNA viruses with a segmented genome. Influenza A viruses can be further categorized into subtypes based on two surface glycoproteins, the hemagglutinin (HA) and the neuraminidase (NA). To date, 16 different HAs and 9 different NAs have been found and may occur in virtually all possible combinations. Free-ranging waterbirds are considered to be the natural reservoir of all influenza A viruses. Even though some mammalian species— humans, pigs, horses and dogs—harbor their own influenza A viruses, there is strong evidence that these mammalian viruses originate from avian influenza A viruses. In addition, avian influenza A viruses may cross the species barrier to other mammals without developing into a stable lineage in the new host species. An example is the outbreak of avian influenza virus of the subtype H7N7 in harbor seals in 1979. Interestingly, the primary replication site for influenza A virus differs between birds and mammals. In birds, the virus replicates primarily in the intestinal tract, whereas in mammals, it replicates primarily in the respiratory tract. An important feature of avian influenza viruses is their capacity to mutate into forms that cause high mortality in poultry. Such mutations only have been recorded for the subtypes H5 and H7 and occur after transmission of these viruses to poultry. Based on their capacity to cause morbidity and mortality in chickens, avian influenza viruses are classified as low pathogenic avian influenza virus (LPAIV) or high pathogenic avian influenza virus (HPAIV)

The pathogenesis of zoonotic viral infections:Lessons learned by studying reservoir hosts

Zoonotic viral infections that cause severe disease or even death in some people may be asymptomatic or mild in reservoir hosts. Comparison of the pathogenesis of these two host categories may potentially explain the difference in disease. However, infections in reservoir hosts are often neglected. Therefore, we compared the pathogenesis of rabies virus, macacine alphaherpesvirus, West Nile virus, Puumala orthohantavirus, monkeypox virus, Lassa mammarenavirus, H5N1 highly pathogenic avian influenza, Marburg virus, Nipah virus, Middle East respiratory syndrome, and simian/human immunodeficiency viruses in both humans and reservoir hosts. We showed that most aspects of the pathogeneses were remarkably similar. The remaining differences lead to the identification of tipping points in the pathogeneses that are important for explaining the disease outcome in severe human cases. Further elucidating these tipping points by studying zoonotic viral infections in their reservoir hosts may teach us how to reduce the severity of zoonotic viral diseases in humans.</p

The neuropathogenesis of highly pathogenic avian influenza H5Nx viruses in mammalian species including humans

Circulation of highly pathogenic avian influenza (HPAI) H5Nx viruses of the A/Goose/Guangdong/1/96 lineage in birds regularly causes infections of mammals, including humans. In many mammalian species, infections are associated with severe neurological disease, a unique feature of HPAI H5Nx viruses compared with other influenza A viruses. Here, we provide an overview of the neuropathogenesis of HPAI H5Nx virus infection in mammals, centered on three aspects: neuroinvasion, neurotropism, and neurovirulence. We focus on in vitro studies, as well as studies on naturally or experimentally infected mammals. Additionally, we discuss the contribution of viral factors to the neuropathogenesis of HPAI H5Nx virus infections and the efficacy of intervention strategies to prevent neuroinvasion or the development of neurological disease.</p

Differential virulence between Asian and African lineages of Zika virus

International audienc

Distribution patterns of influenza virus receptors and viral attachment patterns in the respiratory and intestinal tracts of seven avian species

This study assessed the presence of sialic acid α-2,3 and α-2,6 linked glycan receptors in seven avian species. The respiratory and intestinal tracts of the chicken, common quail, red-legged partridge, turkey, golden pheasant, ostrich, and mallard were tested by means of lectin histochemistry, using the lectins Maackia amurensis agglutinin II and Sambucus nigra agglutinin, which show affinity for α-2,3 and α-2,6 receptors, respectively. Additionally, the pattern of virus attachment (PVA) was evaluated with virus histochemistry, using an avian-origin H4N5 virus and a human-origin seasonal H1N1 virus. There was a great variation of receptor distribution among the tissues and avian species studied. Both α-2,3 and α-2,6 receptors were present in the respiratory and intestinal tracts of the chicken, common quail, red-legged partridge, turkey, and golden pheasant. In ostriches, the expression of the receptor was basically restricted to α-2,3 in both the respiratory and intestinal tracts and in mallards the α-2,6 receptors were absent from the intestinal tract. The results obtained with the lectin histochemistry were, in general, in agreement with the PVA. The differential expression and distribution of α-2,3 and α-2,6 receptors among various avian species might reflect a potentially decisive factor in the emergence of new viral strains

Novel avian-origin influenza A (H7N9) virus attaches to epithelium in both upper and lower respiratory tract of humans

Influenza A viruses from animal reservoirs have the capacity to adapt to humans and cause influenza pandemics. The occurrence of an influenza pandemic requires efficient virus transmission among humans, which is associated with virus attachment to the upper respiratory tract. Pandemic severity depends on virus ability to cause pneumonia, which is associated with virus attachment to the lower respiratory tract. Recently, a novel avian-origin H7N9 influenza A virus with unknown pandemic potential emerged in humans. We determined the pattern of attachment of two genetically engineered viruses containing the hemagglutinin of either influenza virus A/Shanghai/1/13 or A/Anhui/1/13 to formalin-fixed human respiratory tract tissues using histochemical analysis. Our results show that the emerging H7N9 virus attached moderately or abundantly to both upper and lower respiratory tract, a pattern not seen before for avian influenza A viruses. With the caveat that virus attachment is only the first step in the virus replication cycle, these results suggest that the emerging H7N9 virus has the potential both to transmit efficiently among humans and to cause severe pneumonia

Influenza A and B virus attachment to respiratory tract in marine mammals

Patterns of virus attachment to the respiratory tract of 4 marine mammal species were determined for avian and human influenza viruses. Attachment of avian influenza A viruses (H4N5) and (H7N7) and human influenza B viruses to trachea and bronchi of harbor seals is consistent with reported influenza outbreaks in this species