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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 -
Proceedings of the National Academy of... Jun 2019Mononegaviruses are promising tools as oncolytic vectors and transgene delivery vectors for gene therapy and regenerative medicine. By using the Magnet proteins, which...
Mononegaviruses are promising tools as oncolytic vectors and transgene delivery vectors for gene therapy and regenerative medicine. By using the Magnet proteins, which reversibly heterodimerize upon blue light illumination, photocontrollable mononegaviruses (measles and rabies viruses) were generated. The Magnet proteins were inserted into the flexible domain of viral polymerase, and viruses showed strong replication and oncolytic activities only when the viral polymerases were activated by blue light illumination.
Topics: Animals; Cell Line, Tumor; DNA-Directed RNA Polymerases; Genetic Therapy; Genetic Vectors; Humans; Light; Measles virus; Mice, Inbred BALB C; Mice, Nude; Oncolytic Virotherapy; Oncolytic Viruses; Rabies virus; Transgenes; Virus Replication
PubMed: 31138700
DOI: 10.1073/pnas.1906531116 -
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 Sep 2020Viruses have been repurposed into tools for gene delivery by transforming them into viral vectors. The most frequently used vectors are lentiviral vectors (LVs), derived... (Review)
Review
Viruses have been repurposed into tools for gene delivery by transforming them into viral vectors. The most frequently used vectors are lentiviral vectors (LVs), derived from the human immune deficiency virus allowing efficient gene transfer in mammalian cells. They represent one of the safest and most efficient treatments for monogenic diseases affecting the hematopoietic system. LVs are modified with different viral envelopes (pseudotyping) to alter and improve their tropism for different primary cell types. The vesicular stomatitis virus glycoprotein (VSV-G) is commonly used for pseudotyping as it enhances gene transfer into multiple hematopoietic cell types. However, VSV-G pseudotyped LVs are not able to confer efficient transduction in quiescent blood cells, such as hematopoietic stem cells (HSC), B and T cells. To solve this problem, VSV-G can be exchanged for other heterologous viral envelopes glycoproteins, such as those from the Measles virus, Baboon endogenous retrovirus, Cocal virus, Nipah virus or Sendai virus. Here, we provide an overview of how these LV pseudotypes improved transduction efficiency of HSC, B, T and natural killer (NK) cells, underlined by multiple in vitro and in vivo studies demonstrating how pseudotyped LVs deliver therapeutic genes or gene editing tools to treat different genetic diseases and efficiently generate CAR T cells for cancer treatment.
Topics: Animals; CRISPR-Cas Systems; Gene Editing; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Hematopoietic Stem Cells; Humans; Killer Cells, Natural; Lentivirus; Measles virus; Membrane Glycoproteins; Nipah Virus; Research; T-Lymphocytes; Vesicular stomatitis Indiana virus; Viral Envelope Proteins
PubMed: 32933033
DOI: 10.3390/v12091016 -
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 -
Current Opinion in Virology Apr 2020Measles caused an estimated minimum of one million fatalities annually before vaccination. Outstanding progress towards controlling the virus has been made since the... (Review)
Review
Measles caused an estimated minimum of one million fatalities annually before vaccination. Outstanding progress towards controlling the virus has been made since the measles vaccine was introduced, but reduction of measles case-fatalities has stalled at around 100,000 annually for the last decade and a 2019 resurgence in several geographical regions threatens some of these past accomplishments. Whereas measles eradication through vaccination is feasible, a potentially open-ended endgame of elimination may loom. Other than doubling-down on existing approaches, is it worthwhile to augment vaccination efforts with antiviral therapeutics to solve the conundrum? This question is hypothetical at present, since no drugs have yet been approved specifically for the treatment of measles, or infection by any other pathogen of the paramyxovirus family. This article will consider obstacles that have hampered anti-measles and anti-paramyxovirus drug development, discuss MeV-specific challenges of clinical testing, and define drug properties suitable to address some of these problems.
Topics: Animals; Antiviral Agents; Drug Development; Global Health; Humans; Measles; Measles Vaccine; Measles virus
PubMed: 32247280
DOI: 10.1016/j.coviro.2020.02.007 -
Heliyon Jul 2023Over the course of human history, numerous diseases have been caused by the transmission of viruses from an animal reservoir into the human population. The viruses of... (Review)
Review
Over the course of human history, numerous diseases have been caused by the transmission of viruses from an animal reservoir into the human population. The viruses of the genus are human and animal pathogens that emerged from a primordial ancestor a millennia ago and have been transmitting to new hosts, adapting, and evolving ever since. Through interaction with susceptible individuals, as yet undiscovered morbilliviruses or existing morbilliviruses in animal hosts could cause future zoonotic diseases in humans.
PubMed: 37483821
DOI: 10.1016/j.heliyon.2023.e18095 -
Viruses Nov 2019Measles remains a major cause of morbidity and mortality worldwide among vaccine preventable diseases. Recent decline in vaccination coverage resulted in re-emergence of... (Review)
Review
Measles remains a major cause of morbidity and mortality worldwide among vaccine preventable diseases. Recent decline in vaccination coverage resulted in re-emergence of measles outbreaks. Measles virus (MeV) infection causes an acute systemic disease, associated in certain cases with central nervous system (CNS) infection leading to lethal neurological disease. Early following MeV infection some patients develop acute post-infectious measles encephalitis (APME), which is not associated with direct infection of the brain. MeV can also infect the CNS and cause sub-acute sclerosing panencephalitis (SSPE) in immunocompetent people or measles inclusion-body encephalitis (MIBE) in immunocompromised patients. To date, cellular and molecular mechanisms governing CNS invasion are still poorly understood. Moreover, the known MeV entry receptors are not expressed in the CNS and how MeV enters and spreads in the brain is not fully understood. Different antiviral treatments have been tested and validated in vitro, ex vivo and in vivo mainly in small animal models. Most treatments have high efficacy at preventing infection but their effectiveness after CNS manifestations remains to be evaluated. This review describes MeV neural infection and current most advanced therapeutic approaches potentially applicable to treat MeV CNS infection.
Topics: Animals; Antiviral Agents; Central Nervous System; Disease Models, Animal; Encephalitis, Viral; Humans; Measles; Measles virus; Viral Proteins; Viral Tropism
PubMed: 31684034
DOI: 10.3390/v11111017 -
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