pathogenesis
Pathogenesis and ImmunityEarly Transcriptional Changes within Liver, Adrenal Gland, and Lymphoid Tissues Significantly Contribute to Ebola Virus Pathogenesis in Cynomolgus MacaquesEbola virus (EBOV) remains a high-priority pathogen since it continues to cause outbreaks with high case fatality rates. Although it is well established that EBOV results in severe organ damage, our understanding of tissue injury in the liver, adrenal glands, and lymphoid tissues remains limited. We begin to address this knowledge gap by conducting longitudinal gene expression studies in these tissues, which were collected from EBOV-...
Pathogenesis and ImmunityGp37 Regulates the Pathogenesis of Avian Leukosis Virus Subgroup J via Its C TerminusALV-J can cause severe immunosuppression and myeloid leukemia in infected chickens. However, no vaccine or antiviral drug is available against ALV-J, and the mechanism for ALV-J pathogenesis needs to be elucidated. It is generally believed that gp85 and LTR of ALV contribute to its pathogenesis. Here, we found that the C terminus and the tyrosine motifs (YxxM, ITIM, and ITAM-like) in the CTD of Gp37 of ALV-J could...
Virus-Cell InteractionsOvine Herpesvirus 2 Encodes a Previously Unrecognized Protein, pOv8.25, That Targets Mitochondria and Triggers Apoptotic Cell DeathOvine herpesvirus 2 (OvHV-2) circulates among sheep without causing disease. However, upon transmission to cattle, the same virus instigates a frequently lethal disease, malignant catarrhal fever (MCF). While the cause of death and pathogenesis of tissue lesions are still poorly understood, MCF is characterized by the accumulation of lymphocytes in various tissues, associated with vasculitis and cell death. As infectious virus is hardly...
Pathogenesis and ImmunityAn Animal Model That Mimics Human Herpesvirus 6B PathogenesisHuman herpesvirus 6B (HHV-6B) is a ubiquitous virus that establishes lifelong latent infection only in humans, and the infection can reactivate, with severe complications that cause major problems. A small-animal model of HHV-6B infection has thus been desired for research regarding the pathogenicity of HHV-6B and the development of antiviral agents. We generated humanized mice by transplantation with human hematopoietic stem cells, and...
Pathogenesis and Immunity | SpotlightHemagglutinin Stability Regulates H1N1 Influenza Virus Replication and Pathogenicity in Mice by Modulating Type I Interferon Responses in Dendritic CellsDiverse influenza A viruses circulate in wild aquatic birds, occasionally infecting farm animals. Rarely, an avian- or swine-origin influenza virus adapts to humans and starts a pandemic. Seasonal and many universal influenza vaccines target the HA surface protein, which is a key component of pandemic influenza viruses. Understanding the HA properties needed for replication and pathogenicity in mammals may guide response efforts to...
Pathogenesis and ImmunityWhat a Difference a Gene Makes: Identification of Virulence Factors of Cowpox VirusWith the cessation of vaccination against smallpox and its assumed cross-protectivity against other OPV infections, waning immunity could open up new niches for related poxviruses. Therefore, the identification of virulence mechanisms in CPXV is of general interest. Here, we aimed to identify virulence markers in an experimental rodent CPXV infection model using bacterial artificial chromosome (BAC)-based virus recombineering. We...
Pathogenesis and Immunity | SpotlightClearance of Chikungunya Virus Infection in Lymphoid Tissues Is Promoted by Treatment with an Agonistic Anti-CD137 AntibodyAlthough CHIKV causes persistent infection in lymphoid and musculoskeletal tissues in multiple animals, the basis for this is poorly understood, which has hampered pharmacological efforts to promote viral clearance. Here, we evaluated the therapeutic effects on persistent CHIKV infection of an agonistic anti-CD137 MAb that can activate T cell and natural killer cell responses to clear tumors. We show that treatment with anti-CD137 MAb...
Pathogenesis and ImmunityCrimean-Congo Hemorrhagic Fever Mouse Model Recapitulating Human ConvalescenceThe role of antibody or virus-specific T-cell responses in control of acute Crimean-Congo hemorrhagic fever virus infection is largely unclear. This is a critical gap in our understanding of CCHF, and investigation of convalescence following severe acute CCHF has been limited by the lack of suitable small animal models. We report here a mouse model of CCHF in which infected mice develop severe disease but ultimately recover. Although...
Pathogenesis and ImmunityAerosol Transmission of Gull-Origin Iceland Subtype H10N7 Influenza A Virus in FerretsSubtype H10 avian influenza A viruses (IAVs) have caused sporadic human infections and enzootic outbreaks among seals. In the fall of 2015, H10N7 viruses were recovered from gulls in Iceland, and genomic analyses showed that the viruses were genetically related with IAVs that caused outbreaks among seals in Europe a year earlier. These gull-origin viruses showed high binding affinity to human-like glycan receptors. Transmission studies...
Pathogenesis and ImmunityCharacterizing a Murine Model for Astrovirus Using Viral Isolates from Persistently Infected Immunocompromised MiceAstroviruses are widespread in both birds and mammals; however, little is known about the pathogenesis and the immune response to the virus due to the lack of a well-characterized small-animal model. Here we describe two distinct strains of murine astrovirus that cause infections in immunocompetent mice that mirror aspects of asymptomatic human infections, including minimal pathology and short-lived immunity. However, we noted that the...