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Viruses Jul 2016Measles virus is a highly contagious negative strand RNA virus that is transmitted via the respiratory route and causes systemic disease in previously unexposed humans... (Review)
Review
Measles virus is a highly contagious negative strand RNA virus that is transmitted via the respiratory route and causes systemic disease in previously unexposed humans and non-human primates. Measles is characterised by fever and skin rash and usually associated with cough, coryza and conjunctivitis. A hallmark of measles is the transient immune suppression, leading to increased susceptibility to opportunistic infections. At the same time, the disease is paradoxically associated with induction of a robust virus-specific immune response, resulting in lifelong immunity to measles. Identification of CD150 and nectin-4 as cellular receptors for measles virus has led to new perspectives on tropism and pathogenesis. In vivo studies in non-human primates have shown that the virus initially infects CD150⁺ lymphocytes and dendritic cells, both in circulation and in lymphoid tissues, followed by virus transmission to nectin-4 expressing epithelial cells. The abilities of the virus to cause systemic infection, to transmit to numerous new hosts via droplets or aerosols and to suppress the host immune response for several months or even years after infection make measles a remarkable disease. This review briefly highlights current topics in studies of measles virus host invasion and pathogenesis.
Topics: Animals; Host-Pathogen Interactions; Humans; Measles virus; Primates
PubMed: 27483301
DOI: 10.3390/v8080210 -
Viruses Nov 2022The immune system deploys a complex network of cells and signaling pathways to protect host integrity against exogenous threats, including measles virus (MeV). However,... (Review)
Review
The immune system deploys a complex network of cells and signaling pathways to protect host integrity against exogenous threats, including measles virus (MeV). However, throughout its evolutionary path, MeV developed various mechanisms to disrupt and evade immune responses. Despite an available vaccine, MeV remains an important re-emerging pathogen with a continuous increase in prevalence worldwide during the last decade. Considerable knowledge has been accumulated regarding MeV interactions with the innate immune system through two antagonistic aspects: recognition of the virus by cellular sensors and viral ability to inhibit the induction of the interferon cascade. Indeed, while the host could use several innate adaptors to sense MeV infection, the virus is adapted to unsettle defenses by obstructing host cell signaling pathways. Recent works have highlighted a novel aspect of innate immune response directed against MeV unexpectedly involving DNA-related sensing through activation of the cGAS/STING axis, even in the absence of any viral DNA intermediate. In addition, while MeV infection most often causes a mild disease and triggers a lifelong immunity, its tropism for invariant T-cells and memory T and B-cells provokes the elimination of one primary shield and the pre-existing immunity against previously encountered pathogens, known as "immune amnesia".
Topics: Humans; Immune Evasion; Immunity, Innate; Interferons; Measles; Measles virus; Signal Transduction
PubMed: 36560645
DOI: 10.3390/v14122641 -
Virology Journal Mar 2019Canine distemper virus (CDV), currently termed Canine morbillivirus, is an extremely contagious disease that affects dogs. It is identified as a multiple cell tropism... (Review)
Review
BACKGROUND
Canine distemper virus (CDV), currently termed Canine morbillivirus, is an extremely contagious disease that affects dogs. It is identified as a multiple cell tropism pathogen, and its host range includes a vast array of species. As a member of Mononegavirales, CDV has a negative, single-stranded RNA genome, which encodes eight proteins.
MAIN BODY
Regarding the molecular pathogenesis, the hemagglutinin protein (H) plays a crucial role both in the antigenic recognition and the viral interaction with SLAM and nectin-4, the host cells' receptors. These cellular receptors have been studied widely as CDV receptors in vitro in different cellular models. The SLAM receptor is located in lymphoid cells; therefore, the infection of these cells by CDV leads to immunosuppression, the severity of which can lead to variability in the clinical disease with the potential of secondary bacterial infection, up to and including the development of neurological signs in its later stage.
CONCLUSION
Improving the understanding of the CDV molecules implicated in the determination of infection, especially the H protein, can help to enhance the biochemical comprehension of the difference between a wide range of CDV variants, their tropism, and different steps in viral infection. The regions of interaction between the viral proteins and the identified host cell receptors have been elucidated to facilitate this understanding. Hence, this review describes the significant molecular and cellular characteristics of CDV that contribute to viral pathogenesis.
Topics: Animals; Disease Models, Animal; Distemper; Distemper Virus, Canine; Dogs; Hemagglutinins, Viral; Host Microbial Interactions; Host Specificity; Humans; Mice; Nectins; Receptors, Virus; Signaling Lymphocytic Activation Molecule Family Member 1; Viral Proteins; Viral Tropism; Zoonoses
PubMed: 30845967
DOI: 10.1186/s12985-019-1136-6 -
Current Opinion in Virology Feb 2021Effects of measles on the immune system are only partially understood. Lymphoid tissue is a primary site of measles virus (MeV) replication where CD150 is the receptor... (Review)
Review
Effects of measles on the immune system are only partially understood. Lymphoid tissue is a primary site of measles virus (MeV) replication where CD150 is the receptor for infection of both B and T cells. Lymphocyte depletion occurs during the acute phase of infection, but initiation of the adaptive immune response leads to extensive lymphocyte proliferation, production of MeV-specific antibody and T cells, the rash and clearance of infectious virus. Viral RNA persists in lymphoid tissue accompanied by ongoing germinal center proliferation, production of antibody-secreting cells, functionally distinct populations of T cells and antibody avidity maturation to establish life-long immunity. However, at the same time diversity of pre-existing antibodies and numbers of memory and naive B cells are reduced and susceptibility to other infections is increased.
Topics: Adaptive Immunity; Antibodies, Viral; Humans; Immune Tolerance; Immunity, Cellular; Lymphoid Tissue; Measles; Measles virus; Virus Replication
PubMed: 32891958
DOI: 10.1016/j.coviro.2020.08.002 -
Viruses Nov 2019Morbilliviruses are important pathogens, to the point that they have shaped the history of human and animal health [...].
Morbilliviruses are important pathogens, to the point that they have shaped the history of human and animal health [...].
Topics: Animals; Humans; Morbillivirus; Virus Diseases; Virus Internalization; Virus Release; Virus Replication
PubMed: 31703308
DOI: 10.3390/v11111036 -
Viruses Mar 2020Members of the genus are enveloped, negative-strand RNA viruses that include a number of highly contagious pathogens important to humans and animals. They are known to...
Members of the genus are enveloped, negative-strand RNA viruses that include a number of highly contagious pathogens important to humans and animals. They are known to be transmitted via the respiratory route and cause febrile diseases that can be fatal. Despite the availability of attenuated vaccines against several members, these viruses remain responsible for significant morbidity and mortality in their natural hosts worldwide. The development of molecular biology techniques over the past decades has helped increase the understanding of morbillivirus pathogenesis and explore the possibility to engineer their genomes as viral vectors. This Special Issue of explores recent advances in recombinant morbilliviruses platforms, especially measles virus (MV) and canine distemper virus (CDV), for novel vaccine development and oncolytic virotherapy against cancers. Topics in this special issue include parameters involved during the viral vector production, strategies of viral vector engineering, and the underlying mechanisms of the therapeutic effects exhibited by these vectors.
Topics: Genetic Engineering; Genetic Vectors; Humans; Morbillivirus; Oncolytic Virotherapy; Oncolytic Viruses; Vaccines, Attenuated; Viral Vaccines
PubMed: 32245003
DOI: 10.3390/v12030341 -
Viruses Feb 2015Research on morbillivirus infections has led to exciting developments in recent years. Global measles vaccination coverage has increased, resulting in a significant... (Review)
Review
Research on morbillivirus infections has led to exciting developments in recent years. Global measles vaccination coverage has increased, resulting in a significant reduction in measles mortality. In 2011 rinderpest virus was declared globally eradicated - only the second virus to be eradicated by targeted vaccination. Identification of new cellular receptors and implementation of recombinant viruses expressing fluorescent proteins in a range of model systems have provided fundamental new insights into the pathogenesis of morbilliviruses, and their interactions with the host immune system. Nevertheless, both new and well-studied morbilliviruses are associated with significant disease in wildlife and domestic animals. This illustrates the need for robust surveillance and a strategic focus on barriers that restrict cross-species transmission. Recent and ongoing measles outbreaks also demonstrate that maintenance of high vaccination coverage for these highly infectious agents is critical. This introduction briefly summarizes the most important current research topics in this field.
Topics: Animals; Humans; Morbillivirus; Morbillivirus Infections
PubMed: 25685949
DOI: 10.3390/v7020699 -
Veterinary Microbiology Dec 2015Peste des petits ruminants virus causes a highly infectious disease of small ruminants that is endemic across Africa, the Middle East and large regions of Asia. The... (Review)
Review
Peste des petits ruminants virus causes a highly infectious disease of small ruminants that is endemic across Africa, the Middle East and large regions of Asia. The virus is considered to be a major obstacle to the development of sustainable agriculture across the developing world and has recently been targeted by the World Organisation for Animal Health (OIE) and the Food and Agriculture Organisation (FAO) for eradication with the aim of global elimination of the disease by 2030. Fundamentally, the vaccines required to successfully achieve this goal are currently available, but the availability of novel vaccine preparations to also fulfill the requisite for differentiation between infected and vaccinated animals (DIVA) may reduce the time taken and the financial costs of serological surveillance in the later stages of any eradication campaign. Here, we overview what is currently known about the virus, with reference to its origin, updated global circulation, molecular evolution, diagnostic tools and vaccines currently available to combat the disease. Further, we comment on recent developments in our knowledge of various recombinant vaccines and on the potential for the development of novel multivalent vaccines for small ruminants.
Topics: Africa; Animals; Asia; Host Specificity; Middle East; Peste-des-Petits-Ruminants; Peste-des-petits-ruminants virus; Ruminants; Viral Vaccines
PubMed: 26443889
DOI: 10.1016/j.vetmic.2015.08.009 -
Proceedings of the National Academy of... Oct 2022Feline morbillivirus (FeMV) is a recently discovered pathogen of domestic cats and has been classified as a morbillivirus in the family. We determined the complete...
Feline morbillivirus (FeMV) is a recently discovered pathogen of domestic cats and has been classified as a morbillivirus in the family. We determined the complete sequence of FeMV directly from an FeMV-positive urine sample without virus isolation or cell passage. Sequence analysis of the viral genome revealed potential divergence from characteristics of archetypal morbilliviruses. First, the virus lacks the canonical polybasic furin cleavage signal in the fusion (F) glycoprotein. Second, conserved amino acids in the hemagglutinin (H) glycoprotein used by all other morbilliviruses for binding and/or fusion activation with the cellular receptor CD150 (signaling lymphocyte activation molecule [SLAM]/F1) are absent. We show that, despite this sequence divergence, FeMV H glycoprotein uses feline CD150 as a receptor and cannot use human CD150. We demonstrate that the protease responsible for cleaving the FeMV F glycoprotein is a cathepsin, making FeMV a unique morbillivirus and more similar to the closely related zoonotic Nipah and Hendra viruses. We developed a reverse genetics system for FeMV and generated recombinant viruses expressing Venus fluorescent protein from an additional transcription unit located either between the phospho-protein () and matrix () genes or the and large () genes of the genome. We used these recombinant FeMVs to establish a natural infection and demonstrate that FeMV causes an acute morbillivirus-like disease in the cat. Virus was shed in the urine and detectable in the kidneys at later time points. This opens the door for long-term studies to address the postulated role of this morbillivirus in the development of chronic kidney disease.
Topics: Amino Acids; Animals; Cathepsins; Cats; Furin; Hemagglutinins; Humans; Kidney; Morbillivirus; Morbillivirus Infections
PubMed: 36251995
DOI: 10.1073/pnas.2209405119 -
Nature Microbiology Jun 2023Morbilliviruses are among the most contagious viral pathogens of mammals. Although previous metagenomic surveys have identified morbillivirus sequences in bats,...
Morbilliviruses are among the most contagious viral pathogens of mammals. Although previous metagenomic surveys have identified morbillivirus sequences in bats, full-length morbilliviruses from bats are limited. Here we characterize the myotis bat morbillivirus (MBaMV) from a bat surveillance programme in Brazil, whose full genome was recently published. We demonstrate that the fusion and receptor binding protein of MBaMV utilize bat CD150 and not human CD150, as an entry receptor in a mammalian cell line. Using reverse genetics, we produced a clone of MBaMV that infected Vero cells expressing bat CD150. Electron microscopy of MBaMV-infected cells revealed budding of pleomorphic virions, a characteristic morbillivirus feature. MBaMV replication reached 10-10 plaque-forming units ml in human epithelial cell lines and was dependent on nectin-4. Infection of human macrophages also occurred, albeit 2-10-fold less efficiently than measles virus. Importantly, MBaMV is restricted by cross-neutralizing human sera elicited by measles, mumps and rubella vaccination and is inhibited by orally bioavailable polymerase inhibitors in vitro. MBaMV-encoded P/V genes did not antagonize human interferon induction. Finally, we show that MBaMV does not cause disease in Jamaican fruit bats. We conclude that, while zoonotic spillover into humans may theoretically be plausible, MBaMV replication would probably be controlled by the human immune system.
Topics: Animals; Chlorocebus aethiops; Humans; Vero Cells; Chiroptera; Zoonoses; Morbillivirus; Cell Line
PubMed: 37142773
DOI: 10.1038/s41564-023-01380-4