Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in -1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.Peer reviewe

Correction: Recovery of influenza A viruses from lake water and sediments by experimental inoculation

Influenza A viruses (IAV) are zoonotic pathogens relevant to human, domestic animal and wildlife health. Many avian IAVs are transmitted among waterfowl via a faecal-oral-route. Therefore, environmental water where waterfowl congregate may play an important role in the ecology and epidemiology of avian IAV. Water and sediment may sustain and transmit virus among individuals or species. It is unclear at what concentrations waterborne viruses are infectious or remain detectable. To address this, we performed lake water and sediment dilution experiments with varying concentrations or infectious doses of four IAV strains from seal, turkey, duck and gull. To test for infectivity of the IAV strains in a concentration dependent manner, we applied cultivation to specific pathogen free (SPF) embryonated chicken eggs and Madin-Darby Canine Kidney (MDCK) cells. IAV recovery was more effective from embryonated chicken eggs than MDCK cells for freshwater lake dilutions, whereas, MDCK cells were more effective for viral recovery from sediment samples. Low infectious dose (1 PFU/200 μL) was sufficient in most cases to detect and recover IAV from lake water dilutions. Sediment required higher initial infectious doses (≥ 100 PFU/200 μL

Recovery of influenza A viruses from lake water and sediments by experimental inoculation.

Influenza A viruses (IAV) are zoonotic pathogens relevant to human, domestic animal and wildlife health. Many avian IAVs are transmitted among waterfowl via a faecal-oral-route. Therefore, environmental water where waterfowl congregate may play an important role in the ecology and epidemiology of avian IAV. Water and sediment may sustain and transmit virus among individuals or species. It is unclear at what concentrations waterborne viruses are infectious or remain detectable. To address this, we performed lake water and sediment dilution experiments with varying concentrations or infectious doses of four IAV strains from seal, turkey, duck and gull. To test for infectivity of the IAV strains in a concentration dependent manner, we applied cultivation to specific pathogen free (SPF) embryonated chicken eggs and Madin-Darby Canine Kidney (MDCK) cells. IAV recovery was more effective from embryonated chicken eggs than MDCK cells for freshwater lake dilutions, whereas, MDCK cells were more effective for viral recovery from sediment samples. Low infectious dose (1 PFU/200 μL) was sufficient in most cases to detect and recover IAV from lake water dilutions. Sediment required higher initial infectious doses (≥ 100 PFU/200 μL)

Mutations in the H7 HA and PB1 genes of avian influenza a viruses increase viral pathogenicity and contact transmission in guinea pigs

ABSTRACTAvian influenza A viruses (AIV) of the H7 subtype continue to evolve posing a pandemic threat. However, molecular markers of H7N7 AIV pathogenicity and transmission in mammals remain poorly understood. In this study, we performed a systematic in vitro and in vivo analysis by comparing an H7N7 highly pathogenic AIV and its ferret adapted variant. Passaging an H7N7 AIV in ferrets led to six mutations in genes encoding the viral polymerase complex and the viral surface proteins. Here, we show that mutations in the H7 hemagglutinin gene cause increased pathogenicity in mice. Contact transmission between guinea pigs required additional mutations in the gene encoding the polymerase subunit PB1. Thus, particular vigilance is required with respect to HA and PB1 mutations as predictive molecular markers to assess the pandemic risk posed by emerging H7 avian influenza viruses

Evolution of 2009 H1N1 influenza viruses during the pandemic correlates with increased viral pathogenicity and transmissibility in the ferret model.

There is increasing evidence that 2009 pandemic H1N1 influenza viruses have evolved after pandemic onset giving rise to severe epidemics in subsequent waves. However, it still remains unclear which viral determinants might have contributed to disease severity after pandemic initiation. Here, we show that distinct mutations in the 2009 pandemic H1N1 virus genome have occurred with increased frequency after pandemic declaration. Among those, a mutation in the viral hemagglutinin was identified that increases 2009 pandemic H1N1 virus binding to human-like α2,6-linked sialic acids. Moreover, these mutations conferred increased viral replication in the respiratory tract and elevated respiratory droplet transmission between ferrets. Thus, our data show that 2009 H1N1 influenza viruses have evolved after pandemic onset giving rise to novel virus variants that enhance viral replicative fitness and respiratory droplet transmission in a mammalian animal model. These findings might help to improve surveillance efforts to assess the pandemic risk by emerging influenza viruses

Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice

Pregnant women are at high risk for severe influenzadisease outcomes, yet insights into the underlyingmechanisms are limited. Here, we present models ofH1N1 infection in syngenic and allogenic pregnantmice; infection in the latter mirrors the severe courseof 2009 pandemic influenza in pregnant women. Wefound that the anti-viral immune response in the pregnanthost was significantly restricted as compared tothe non-pregnant host. This included a reduced type Iinterferon response as well as impaired migration ofCD8+ T cells into the lung. The multi-faceted failureto mount an anti-viral response in allogenic pregnantmice resulted in a less stringent selective environmentthat promoted the emergence of 2009 H1N1 virusvariants that specifically counteract type I interferonresponse and mediate increased viral pathogenicity.These insights underscore the importance of influenzavaccination compliance in pregnant womenand may open novel therapeutic avenues.Fil: Engels, Géraldine. University Medical Center Hamburg-Eppendorf; Alemania. Leibniz Institut Für Experimentelle Virologie; AlemaniaFil: Hierweger, Alexandra Maximiliane. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Hoffmann, Julia. Leibniz Institut Für Experimentelle Virologie; AlemaniaFil: Thieme, René. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Thiele, Swantje. Leibniz Institut Für Experimentelle Virologie; AlemaniaFil: Bertram, Stephanie. Leibniz Institut Für Experimentelle Virologie; AlemaniaFil: Dreier, Carola. Leibniz Institut Für Experimentelle Virologie; AlemaniaFil: Resa-Infante, Patricia. Leibniz Institut Für Experimentelle Virologie; AlemaniaFil: Jacobsen, Henning. Leibniz Institut Für Experimentelle Virologie; AlemaniaFil: Thiele, Kristin. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Alawi, Malik. Leibniz Institut Für Experimentelle Virologie; AlemaniaFil: Indenbirken, Daniela. Leibniz Institut Für Experimentelle Virologie; AlemaniaFil: Grundhoff, Adam. Leibniz Institut Für Experimentelle Virologie; AlemaniaFil: Siebels, Svenja. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Fischer, Nicole. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Stojanovska, Violeta. University of Groningen; Países BajosFil: Muzzio, Damián Oscar. University of Greifswald; AlemaniaFil: Jensen, Cristian Federico. University of Greifswald; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Karimi, Khalil. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Mittrücker, Hans-Willi. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Arck, Petra Clara. University Medical Center Hamburg-Eppendorf; AlemaniaFil: Gabriel, Gülsah. Leibniz Institut Für Experimentelle Virologie; Alemani

In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study

Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation