Chronic infection of domestic cats with feline morbillivirus, United States

Letter [No abstract available

Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease

Canine distemper virus (CDV) causes systemic infection resulting in severe and often fatal disease in a large spectrum of animal host species. The virus is closely related to measles virus and targets myeloid, lymphoid, and epithelial cells, but CDV is more virulent and the infection spreads more rapidly within the infected host. Here, we aimed to study the pathogenesis of wild-type CDV infection by experimentally inoculating ferrets with recombinant CDV (rCDV) based on an isolate directly obtained from a naturally infected raccoon. The recombinant virus was engineered to express a fluorescent reporter protein, facilitating assessment of viral tropism and virulence. In ferrets, this wild type-based rCDV infected myeloid, lymphoid, and epithelial cells, and the infection resulted in systemic dissemination to multiple tissues and organs, especially those of the lymphatic system. High infection percentages in immune cells resulted in depletion of these cells both from circulation and from lymphoid tissues. The majority of CDV-infected ferrets reached their humane endpoints within 20 d and had to be euthanized. In that period, the virus also reached the central nervous system in several ferrets, but we did not observe the development of neurological complications during the study period of 23 d. Two out of 14 ferrets survived CDV infection and developed neutralizing antibodies. We show for the first time the pathogenesis of a non-adapted wild type-based rCDV in ferrets. IMPORTANCE Infection of ferrets with recombinant canine distemper virus (rCDV) expressing a fluorescent reporter protein has been used as proxy to understand measles pathogenesis and immune suppression in humans. CDV and measles virus use the same cellular receptors, but CDV is more virulent, and infection is often associated with neurological complications. rCDV strains in current use have complicated passage histories, which may have affected their pathogenesis. Here, we studied the pathogenesis of the first wild type-based rCDV in ferrets. We used macroscopic fluorescence to identify infected cells and tissues; multicolor flow cytometry to determine viral tropism in immune cells; and histopathology and immunohistochemistry to characterize infected cells and lesions in tissues. We conclude that CDV often overwhelmed the immune system, resulting in viral dissemination to multiple tissues in the absence of a detectable neutralizing antibody response. This virus is a promising tool to study the pathogenesis of morbillivirus infections.</p

Inoculation of raccoons with a wild-type-based recombinant canine distemper virus results in viremia, lymphopenia, fever, and widespread histological lesions

Raccoons are naturally susceptible to canine distemper virus (CDV) infection and can be a potential source of spill-over events. CDV is a highly contagious morbillivirus that infects multiple species of carnivores and omnivores, resulting in severe and often fatal disease. Here, we used a recombinant CDV (rCDV) based on a full-genome sequence detected in a naturally infected raccoon to perform pathogenesis studies in raccoons. Five raccoons were inoculated intratracheally with a recombinant virus engineered to express a fluorescentreporter protein, and extensive virological, serological, histological, and immunohistochemical assessments were performed at differenttime points post inoculation. rCDV-infected white blood cells were detected as early as 4 days post inoculation (dpi). Raccoon necropsies at 6 and 8 dpi revealed replication in the lymphoid tissues, preceding spread into peripheral tissues observed during necropsies at 21 dpi. Whereas lymphocytes, and to a lesser extent myeloid cells, were the main target cells of CDV at early time points, CDV additionally targeted epithelia at 21 dpi. At this later time point, CDV-infected cells were observed throughout the host. We observed lymphopenia and lymphocyte depletion from lymphoid tissues after CDV infection, in the absence of detectable CDV neutralizing antibodies and an impaired ability to clear CDV, indicating that the animals were severely immunosuppressed. The use of a wild-type-based recombinant virus in a natural host species infection study allowed systematic and sensitive assessment of antigen detection by immunohistochemistry, enabling further comparative pathology studies of CDV infection in differentspecies.</p

Targeting spike glycans to inhibit SARS-CoV2 viral entry

SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety of biophysical approaches, we demonstrate that the interaction is avidity driven and that BOA cross-links the spike protein into soluble aggregates. Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that multivalent glycan-targeting molecules have the potential to act as pan-coronavirus inhibitors

Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease

Canine distemper virus (CDV) causes systemic infection resulting in severe and often fatal disease in a large spectrum of animal host species. The virus is closely related to measles virus and targets myeloid, lymphoid, and epithelial cells, but CDV is more virulent and the infection spreads more rapidly within the infected host. Here, we aimed to study the pathogenesis of wild-type CDV infection by experimentally inoculating ferrets with recombinant CDV (rCDV) based on an isolate directly obtained from a naturally infected raccoon. The recombinant virus was engineered to express a fluorescent reporter protein, facilitating assessment of viral tropism and virulence. In ferrets, this wild type-based rCDV infected myeloid, lymphoid, and epithelial cells, and the infection resulted in systemic dissemination to multiple tissues and organs, especially those of the lymphatic system. High infection percentages in immune cells resulted in depletion of these cells both from circulation and from lymphoid tissues. The majority of CDV-infected ferrets reached their humane endpoints within 20 d and had to be euthanized. In that period, the virus also reached the central nervous system in several ferrets, but we did not observe the development of neurological complications during the study period of 23 d. Two out of 14 ferrets survived CDV infection and developed neutralizing antibodies. We show for the first time the pathogenesis of a non-adapted wild type-based rCDV in ferrets. IMPORTANCE Infection of ferrets with recombinant canine distemper virus (rCDV) expressing a fluorescent reporter protein has been used as proxy to understand measles pathogenesis and immune suppression in humans. CDV and measles virus use the same cellular receptors, but CDV is more virulent, and infection is often associated with neurological complications. rCDV strains in current use have complicated passage histories, which may have affected their pathogenesis. Here, we studied the pathogenesis of the first wild type-based rCDV in ferrets. We used macroscopic fluorescence to identify infected cells and tissues; multicolor flow cytometry to determine viral tropism in immune cells; and histopathology and immunohistochemistry to characterize infected cells and lesions in tissues. We conclude that CDV often overwhelmed the immune system, resulting in viral dissemination to multiple tissues in the absence of a detectable neutralizing antibody response. This virus is a promising tool to study the pathogenesis of morbillivirus infections

Inoculation of raccoons with a wild-type-based recombinant canine distemper virus results in viremia, lymphopenia, fever, and widespread histological lesions

Raccoons are naturally susceptible to canine distemper virus (CDV) infection and can be a potential source of spill-over events. CDV is a highly contagious morbillivirus that infects multiple species of carnivores and omnivores, resulting in severe and often fatal disease. Here, we used a recombinant CDV (rCDV) based on a full-genome sequence detected in a naturally infected raccoon to perform pathogenesis studies in raccoons. Five raccoons were inoculated intratracheally with a recombinant virus engineered to express a fluorescent reporter protein, and extensive virological, serological, histological, and immunohistochemical assessments were performed at different time points post inoculation. rCDV-infected white blood cells were detected as early as 4 days post inoculation (dpi). Raccoon necropsies at 6 and 8 dpi revealed replication in the lymphoid tissues, preceding spread into peripheral tissues observed during necropsies at 21 dpi. Whereas lymphocytes, and to a lesser extent myeloid cells, were the main target cells of CDV at early time points, CDV additionally targeted epithelia at 21 dpi. At this later time point, CDV-infected cells were observed throughout the host. We observed lymphopenia and lymphocyte depletion from lymphoid tissues after CDV infection, in the absence of detectable CDV neutralizing antibodies and an impaired ability to clear CDV, indicating that the animals were severely immunosuppressed. The use of a wild-type-based recombinant virus in a natural host species infection study allowed systematic and sensitive assessment of antigen detection by immunohistochemistry, enabling further comparative pathology studies of CDV infection in different species. IMPORTANCE Expansion of the human interface supports increased interactions between humans and peridomestic species like raccoons. Raccoons are highly susceptible to canine distemper virus (CDV) and are considered an important target species. Spill-over events are increasingly likely, potentially resulting in fatal CDV infections in domestic and free ranging carnivores. CDV also poses a threat for (non-human) primates, as massive outbreaks in macaque colonies were reported. CDV pathogenesis was studied by experimental inoculation of several species, but pathogenesis in raccoons was not properly studied. Recently, we generated a recombinant virus based on a full-genome sequence detected in a naturally infected raccoon. Here, we studied CDV pathogenesis in its natural host species and show that distemper completely overwhelms the immune system and spreads to virtually all tissues, including the central nervous system. Despite this, raccoons survived up to 21 d post inoculation with long-term shedding, supporting an important role of raccoons as host species for CDV

Disease: A Hitherto Unexplored Constraint on the Spread of Dogs (Canis lupus familiaris) in Pre-Columbian South America

Although debate continues, there is agreement that dogs (Canis lupus familiaris) were first domesticated in Eurasia, spreading from there to other parts of the world. However, while that expansion already extended as far as Europe, China, and North America by the early Holocene, dogs spread into (and south of) the tropics only much later. In South America, for example, the earliest well attested instances of their presence do not reach back much beyond 3000 cal. BC, and dogs were still absent from large parts of the continent – Amazonia, the Gran Chaco, and much of the Southern Cone – at European contact. Previous explanations for these patterns have focused on cultural choice, the unsuitability of dogs for hunting certain kinds of tropical forest prey, and otherwise unspecified environmental hazards, while acknowledging that Neotropical lowland forests witness high rates of canine mortality. Building on previous work in Sub-Saharan Africa (Mitchell 2015) and noting that the dog’s closest relatives, the grey wolf (C. lupus) and the coyote (C. latrans), were likewise absent from South and most of Central America in Pre- Columbian times, this paper explores instead the possibility that infectious disease constrained the spread of dogs into Neotropical environments. Four diseases are considered, all likely to be native and/or endemic to South America: canine distemper, canine trypanosomiasis, canine rangeliosis, and canine visceral leishmaniasis caused by infection with Leishmania amazonensis and L. colombiensis. The paper concludes by suggesting ways in which the hypothesis that disease constrained the expansion of dogs into South America can be developed further

Mapping the evolutionary trajectories of morbilliviruses: What, where and whither

Morbilliviruses are pathogens of humans and other animals. Live attenuated morbillivirus vaccines have been used to end endemic transmission of measles virus (MV) in many parts of the developed world and to eradicate rinderpest virus. Entry is mediated by two different receptors which govern virus lymphotropism and epitheliotropism. Morbillivirus transmissibility is unparalleled and MV represents the most infectious human pathogen on earth. Their evolutionary origins remain obscure and their potential for adaption to new hosts is poorly understood. It has been suggested that MV could be eradicated. Therefore it is imperative to dissect barriers which restrict cross species infections. This is important as ecological studies identify novel morbilliviruses in a vast number of small mammals and carnivorous predators