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Influenza is a major public health concern causing millions of hospitalizations every year. Either type A (IAV) or B (IBV) viruses can cause the diseases. While IAV is generally the predominant circulating virus, IBV can be more dominant than IAV in a given season. The current seasonal vaccines need to be updated annually based on prediction of the likely strains in the upcoming season. However, mismatches between vaccine strains and the actual circulating viruses can occur because of the remarkably high rate of mutation in the viral surface glycoprotein, hemagglutinin (HA), reducing vaccine effectiveness significantly. HA consists of two subunits, HA1 and HA2, where HA1 evolves in an unpredictable fashion while HA2 is highly conserved. Previously, we identified a 14-aa fusion peptide sequence at the N-terminus of HA2 that is universally conserved in IAV and IBV. Antibody against this epitope was able to bind and quantify multiple influenza viruses as well as cross-neutralize multiple subtypes of IAV. Here, we show that the universal antibody induces robust antibody-dependent cellular cytotoxicity (ADCC) against diverse influenza viruses, including human and avian IAVs as well as both lineages of IBV. These results revealed the versatile effector functions of this universal antibody. Funding Information: This work was supported by the Government of Canada. Declaration of Interests: The authors declare no conflict of interest.

Outcomes of Zika virus (ZIKV) infection in pregnant women vary from the birth of asymptomatic offspring to abnormal development and severe brain lesions in fetuses and infants. There are concerns that offspring affected in utero and born without apparent symptoms may develop mental illnesses. Therefore, animal models are important to test interventions against in utero infection and health sequelae in symptomatic and likely more widespread asymptomatic offspring. To partially reproduce in utero infection in humans, we directly inoculated selected porcine conceptuses with ZIKV. Inoculation resulted in rapid trans-fetal infections, persistent infection in conceptuses, molecular pathology in fetal brains, fetal antibody and type I interferon responses. Offspring infected in utero showed ZIKV in their fetal membranes collected after birth. Some in utero affected piglets were small, depressed, had undersized brains, and showed seizures. Some piglets showed potentially increased activity. Our data suggest that porcine model of persistent in utero ZIKV infection has a strong potential for translational research and can be used to test therapeutic interventions in vivo., Highlights • Zika virus (ZIKV) causes persistent infection in porcine conceptuses. • The established fetal model can be used to test therapeutic interventions against ZIKV in vivo. • In utero ZIKV infection may impair health in porcine offspring. Zika virus (ZIKV) has recently emerged and spread in the Americas. The virus infects pregnant women and causes, in some cases, debilitating brain lesions in fetuses and newborns. The majority of infections, however, do not cause visible abnormalities in mothers and infants. In this study, we induced ZIKV infection in fetal pigs. Similar to humans, ZIKV caused prolonged (for months) infection in porcine fetuses. Some newborn animals also developed several abnormalities previously observed in human infants. Pigs and humans have a high similarity in anatomy, physiology, and immunity and can be used for ZIKV studies to benefit human health.

It is a common laboratory practice to propagate viruses in cell culture. While convenient, these methodologies often result in unintentional genetic alterations, which have lead to adaptation and even attenuation in animal models of disease. An example is the attenuation of hantaviruses (family: Bunyaviridae, genus: Hantavirus) when cultured in vitro. In this case, viruses propagated in the natural reservoir species cause disease in nonhuman primates that closely mimics the human disease, but passaging in cell culture attenuates these viruses to the extent that do not cause any measurable disease in nonhuman primates. As efforts to develop animal models progress, it will be important to take into account the influences that culture in vitro may have on the virulence of viruses. In this review we discuss this phenomenon in the context of past and recent examples in the published literature.

Due to the increase of Zika virus (ZIKV) transmission throughout the world, many commercial kits have recently become available to aid in laboratory diagnosis of ZIKV infections in clinical samples. Here, we analyze the fully automated Liaison® XL Zika Capture immunoglobulin M (IgM) assay against the recommended IgM-capture enzyme-linked immunosorbent assay.

Exotic and emerging viral pathogens associated with high morbidity and mortality in humans are being identified annually with recent examples including Lujo virus in southern Africa, Severe Fever with Thrombocytopenia Syndrome virus in China and a SARS-like coronavirus in the Middle East. The sporadic nature of these infections hampers our understanding of these diseases and limits the opportunities to design appropriate medical countermeasures against them. Because of this, animal models are utilized to gain insight into the pathogenesis of disease with the overall goal of identifying potential targets for intervention and evaluating specific therapeutics and vaccines. For these reasons it is imperative that animal models of disease recapitulate the human condition as closely as possible in order to provide the best predictive data with respect to the potential efficacy in humans. In this article we review the current status of disease models for highly pathogenic and emerging viral pathogens.

Hantavirus pulmonary syndrome (HPS) is a relatively rare, but frequently fatal disease associated with New World hantaviruses, most commonly Sin Nombre and Andes viruses in North and South America, respectively. It is characterized by fever and the sudden, rapid onset of severe respiratory distress and cardiogenic shock, which can be fatal in up to 50% of cases. Currently there are no approved antiviral therapies or vaccines for the treatment or prevention of HPS. A major obstacle in the development of effective medical countermeasures against highly pathogenic agents like the hantaviruses is recapitulating the human disease as closely as possible in an appropriate and reliable animal model. To date, the only animal model that resembles HPS in humans is the Syrian hamster model. Following infection with Andes virus, hamsters develop HPS-like disease which faithfully mimics the human condition with respect to incubation period and pathophysiology of disease. Perhaps most importantly, the sudden and rapid onset of severe respiratory distress observed in humans also occurs in hamsters. The last several years has seen an increase in studies utilizing the Andes virus hamster model which have provided unique insight into HPS pathogenesis as well as potential therapeutic and vaccine strategies to treat and prevent HPS. The purpose of this article is to review the current understanding of HPS disease progression in Syrian hamsters and discuss the suitability of utilizing this model to evaluate potential medical countermeasures against HPS.

The Syrian golden hamster (Mesocricetus auratus) is a valuable but under-utilized animal model for studies of human viral pathogens such as bunyaviruses, arenaviruses, flaviviruses, henipaviruses, and SARS-coronavirus. A lack of suitable reagents and specific assays for monitoring host responses has limited the use of this animal model to clinical observations, pathology and humoral immune responses. The objective of this study was to establish and validate assays to monitor host immune responses in the hamster including important pro-inflammatory, anti-inflammatory and innate immune responses, as well as markers of apoptosis, cell proliferation, cell junction integrity and coagulation. Commercially available mouse and rat ELISA and luminex panels were screened for potential cross-reactivity, but were found to be of limited value for studying host responses in hamsters. Subsequently, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays for the detection of 51 immune-related and four internal reference genes were developed. To validate the immune-related assays, hamsters were infected with vesicular stomatitis virus (VSV), Indiana species, or treated with lipopolysaccharide (LPS) and host immune responses were monitored in selected organs. Ribosomal protein L18 was identified as the most stable internal reference gene. In conclusion, these new assays will greatly improve the use of the hamster as an important small animal model in infectious disease research.

Varicella-zoster vaccine is a live attenuated virus. It is, therefore, necessary to have a test to differentiate vaccine from wild-type varicella-zoster virus (VZV) strains for the investigation of varicella or zoster-like rash illness in individuals vaccinated previously. In addition, it is necessary to have a rapid VZV assay for use in the context of smallpox bioterrorism laboratory testing. Using specific primers and hybridization probes, a rapid method to differentiate vaccine strain VZV from wild-type VZV was developed based on the presence or absence of a Pst I restriction site within open reading frame (ORF) 38. Using this ORF 38 assay in conjunction with a similar previously described ORF 62 assay allows for further differentiation of vaccine strain, wild-type and a laboratory control strain (Ellen) VZV. This is accomplished because Ellen VZV is similar to wild-type VZV with respect to the ORF 38 assay but is similar to vaccine strain VZV with respect to the ORF 62 assay. The hybridization probes for each ORF are labeled with different fluorescent tags thus allowing both assays to be run simultaneously in a single tube. Both assays demonstrate a high degree of specificity for VZV and can reliably detect between 10 and 100 copies of VZV DNA. Thus, the real-time polymerase chain reaction (PCR) assay for VZV described below provides a rapid assay allowing the simultaneous differentiation of vaccine, wild-type and laboratory control strains of VZV.