-
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 -
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 -
Human Vaccines & Immunotherapeutics 2015Measles was an inevitable infection during the human development with substantial degree of morbidity and mortality. The severity of measles virus (MV) infection was... (Review)
Review
Measles was an inevitable infection during the human development with substantial degree of morbidity and mortality. The severity of measles virus (MV) infection was largely contained by the development of a live attenuated vaccine that was introduced into the vaccination programs. However, all efforts to eradicate the disease failed and continued to annually result in significant deaths. The development of molecular biology techniques allowed the rescue of MV from cDNA that enabled important insights into a variety of aspects of the biology of the virus and its pathogenesis. Subsequently these technologies facilitated the development of novel vaccine candidates that induce immunity against measles and other pathogens. Based on the promising prospective, the use of MV as a recombinant vaccine and a therapeutic vector is addressed.
Topics: Drug Carriers; Genetic Vectors; Humans; Measles; Measles Vaccine; Measles virus; Oncolytic Virotherapy; Vaccines, Attenuated; Vaccines, Synthetic
PubMed: 25483511
DOI: 10.4161/hv.34298 -
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 -
Current Opinion in Virology Apr 2020Clearance of measles virus is complex. Infectious virus is cleared by the adaptive immune response manifested by the characteristic maculopapular rash. CD8 T cells are... (Review)
Review
Clearance of measles virus is complex. Infectious virus is cleared by the adaptive immune response manifested by the characteristic maculopapular rash. CD8 T cells are major effectors of infectious virus clearance, a process that may fail in individuals with compromised cellular immune responses leading to progressive giant cell pneumonia and/or measles inclusion body encephalitis. In contrast to the usual rapid clearance of infectious virus, clearance of viral RNA is slow with persistence in lymphoid tissue for many months. Persistence of MeV RNA may contribute to the late development of the slowly progressive disease subacute sclerosing panencephalitis in children infected at a young age and to measles-associated immune suppression but also to maturation of the immune response and development of life-long immunity.
Topics: Animals; CD8-Positive T-Lymphocytes; Humans; Measles; Measles virus; RNA, Viral
PubMed: 32387998
DOI: 10.1016/j.coviro.2020.03.003 -
Advances in Respiratory Medicine 2019Measles is an acute febrile illness, potentially fatal and highly contagious, which is transmitted through the respiratory mode. Fever combined with one of the...
Measles is an acute febrile illness, potentially fatal and highly contagious, which is transmitted through the respiratory mode. Fever combined with one of the following: cough, coryza, conjunctivitis are the first manifestations of the disease. Koplik's spots may also appear on the buccal mucosa providing an opportunity to set the diagnosis even before the emergence of rash. Rash typically appears 3-4 days after the onset of fever, initially on the face and behind the ears, and its appearance is associated with the peak of the symptoms. Measles affects multiple systems, including the respiratory system, with pneumonia being one of the most lethal complications. Management involves best supportive care, correction of dehydration and nutritional deficiencies, treatment of secondary bacterial infections and provision of vitamin A. Importantly, given that measles present with lifelong immunity following infection or vaccination, prevention through measles vaccination has a cardinal role for measles' elimination. Indeed, public education and vaccination led to an estimated 79% decrease in global measles deaths from 2000 to 2015. Nonetheless, the last two years have seen a measles outbreak in several countries, partially due to the anti-vaccination movement. This article aims to present two cases of measles in our hospital and highlight the pressing need for vaccination in order to eradicate a potentially fatal disease.
Topics: Female; Glucocorticoids; Humans; Male; Measles; Measles Vaccine; Measles virus; Middle Aged; Mouth Mucosa; Pneumonia, Viral
PubMed: 30830960
DOI: 10.5603/ARM.a2019.0010 -
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 -
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