Distribution of measles virus in the central nervous system  of HIV-seropositive children

McQuaid, Stephen; Cosby, S. L.; Koffi, K.; Hondé, M.; Kirk, John M.; Lucas, Sebastian

doi:10.1007/s004010050945

Cited by 36 publications

(30 citation statements)

References 26 publications

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“…Among those, postinfectious encephalomyelitis occurs in 1 in 1,000 cases within weeks of acute measles, but the extent of viral replication seems minor and the pathology is immune mediated (14,32). On the other hand, extensive viral replication was documented in the context of a rare fatal course of the acute disease (24,30), and two chronic manifestations, measles inclusion body encephalitis and subacute sclerosing panencephalitis (SSPE) (5). The former occurs between 2 and 6 months after acute infection and is limited to individuals with an innate immune defect resulting in an inability to clear the virus during acute infection and subsequent persistence in the CNS (16,32).…”

Section: Discussionmentioning

confidence: 99%

Canine Distemper Virus Uses both the Anterograde and the Hematogenous Pathway for Neuroinvasion

Rudd

Cattaneo

Messling

2006

J Virol

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Canine distemper virus (CDV), a member of the Morbillivirus genus that also includes measles virus, frequently causes neurologic complications, but the routes and timing of CDV invasion of the central nervous system (CNS) are poorly understood. To characterize these events, we cloned and sequenced the genome of a neurovirulent CDV (strain A75/17) and produced an infectious cDNA that expresses the green fluorescent protein. This virus fully retained its virulence in ferrets: the course and signs of disease were equivalent to those of the parental isolate. We observed CNS invasion through two distinct pathways: anterogradely via the olfactory nerve and hematogenously through the choroid plexus and cerebral blood vessels. CNS invasion only occurred after massive infection of the lymphatic system and spread to the epithelial cells throughout the body. While at early time points, mostly immune and endothelial cells were infected, the virus later spread to glial cells and neurons. Together, the results suggest similarities in the timing, target cells, and CNS invasion routes of CDV, members of the Morbillivirus genus, and even other neurovirulent paramyxoviruses like Nipah and mumps viruses.Canine distemper virus (CDV) and the closely related viruses that infect marine mammals have the highest incidence of central nervous system (CNS) complications among viruses of the genus Morbillivirus. Up to 30% of dogs exhibit signs of neurologic involvement during or after CDV infection, and most wild carnivores that succumb to CDV have some evidence of CNS infection (8,18,20,38,51). With 1 in 1,000 cases, the neurovirulent potential of measles virus (MV) is comparatively lower, but CNS complications remain one of the main problems associated with MV infections in countries with an established health care system (32). Because of its relatively high degree of neurovirulence and the availability of a sensitive small animal model, CDV is an ideal candidate to characterize the events involved in morbillivirus neuroinvasion.All morbilliviruses display a strong lymphotropism, which correlates with the presence of their principal receptor, the signaling lymphocytic activation molecule (SLAM, CD150), on a variety of immune cells (6,36,40). In ferrets infected with a virulent CDV strain, more than 50% of circulating peripheral blood mononuclear cells (PBMC) contain infectious virus, and up to 10% of PBMC in MV-infected monkeys are virus positive (46, 53). Because of these findings and the fact that morbilliviruses are highly cell associated, it is thought that the contact between virus and CNS occurs through infected PBMC. Previous studies of typical wild-type isolates like strain A75/17 in dogs further support this theory (38).At the onset of the symptomatic disease around 14 days after intranasal inoculation, infected cells are predominantly detected in the perivascular spaces of the CNS, the choroid plexus, and the ependyma (19,39). Around 3 weeks after infection, CDV-positive glial cells and neurons are found in the white matter, and...

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Section: Discussionmentioning

confidence: 99%

Canine Distemper Virus Uses both the Anterograde and the Hematogenous Pathway for Neuroinvasion

Rudd

Cattaneo

Messling

2006

J Virol

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“…MV antigen in formalin-fixed human corneal rim tissue was detected using a mAb (diluted 1 : 1000) to the MV N protein (Harlan Seralabs) as described previously (McQuaid et al, 1998). Formalin-fixed tissue samples taken from rMV IC323 EGFPinfected rhesus and cynomolgus macaques euthanized at 9 days p.i.…”

Section: Discussionmentioning

confidence: 99%

Wild-type measles virus infection of primary epithelial cells occurs via the basolateral surface without syncytium formation or release of infectious virus

Ludlow

Rennick

Sarlang

et al. 2009

Journal of General Virology

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The lymphotropic and myelotropic nature of wild-type measles virus (wt-MV) is well recognized, with dendritic cells and lymphocytes expressing the MV receptor CD150 mediating systemic spread of the virus. Infection of respiratory epithelial cells has long been considered crucial for entry of MV into the body. However, the lack of detectable CD150 on these cells raises the issue of their importance in the pathogenesis of measles. This study utilized a combination of in vitro, ex vivo and in vivo model systems to characterize the susceptibility of epithelial cells to wt-MV of proven pathogenicity. Low numbers of MV-infected epithelial cells in close proximity to underlying infected lymphocytes or myeloid cells suggested infection via the basolateral side of the epithelium in the macaque model. In primary cultures of human bronchial epithelial cells, foci of MV-infected cells were only observed following infection via the basolateral cell surface. The extent of infection in primary cells was enhanced both in vitro and in ex vivo cornea rim tissue by disrupting the integrity of the cells prior to the application of virus. This demonstrated that, whilst epithelial cells may not be the primary target cells for wt-MV, areas of epithelium in which tight junctions are disrupted can become infected using high m.o.i. The low numbers of MV-infected epithelial cells observed in vivo in conjunction with the absence of infectious virus release from infected primary cell cultures suggest that epithelial cells have a peripheral role in MV transmission. INTRODUCTIONMeasles is a severe disease contributing to significant morbidity and mortality rates in many parts of the developing world (Grais et al., 2007). It is also of growing concern in some areas of the developed world where the vaccination rate has fallen below the level required to prevent periodic outbreaks of measles (Choi et al., 2008). The disease is characterized by fever and a maculopapular rash, often in conjunction with cough, coryza and/or conjunctivitis, and a generalized immunosuppression. The causative agent, wild-type measles virus (wt-MV) is spread by aerosolized droplets or direct contact (Griffin, 2007). The highly infectious nature of MV not only suggests a very efficient route of entry into the body but also an effective means of dissemination to susceptible individuals following systemic spread of the virus within the body.The tropism of MV in vivo is determined mainly by the distribution of CD150, also known as signalling lymphocyte activation molecule (SLAM), which is the primary cellular receptor for wild-type strains of the virus. The molecule is widely expressed in lymphoid tissues on subsets of B and T lymphocytes, thymocytes, macrophages and dendritic cells (DCs) (Kruse et al., 2001;McQuaid & Cosby, 2002). This is reflected by analysis of MV-infected cell types present at different stages of the disease, which shows that, in all tissues involved, the majority of infected cells are of a lymphoid origin (Hall et al., 1971; Moench et al., 1988). Ano...

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“…This fatal neurological disease caused by MV still occurs among immunocompromised patients (16,37,40), particularly in children infected with HIV (6,35,44). In some rare cases, vaccinal virus could also be involved in the pathogenesis of MV encephalitis (51).…”

Section: Discussionmentioning

confidence: 99%

“…Histologically, this progressive infectious encephalitis is characterized by (i) the presence of intracellular inclusion bodies which contain paramyxovirus nucleocapsids and (ii) sparseness of brain inflammation (43). Although measles vaccination significantly decreased the number of cases of the first two forms of MVinduced encephalitis, the third form remains problematic in an increasing population of immunocompromised patients (16,37,40) and has reemerged particularly in children infected with human immunodeficiency virus (HIV) (6,35,44).Appropriate animal models are needed to analyze MV-induced pathology. Initially, rodents were shown to be susceptible to MV brain infection (30).…”

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confidence: 99%

Productive Measles Virus Brain Infection and Apoptosis in CD46 Transgenic Mice

Evlashev

Moyse

Valentin

et al. 2000

J Virol

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Measles virus (MV) infection causes acute childhood disease, associated in certain cases with infection of the central nervous system (CNS) and development of neurological disease.To develop a murine model of MV-induced pathology, we generated several lines of transgenic mice ubiquitously expressing as the MV receptor a human CD46 molecule with either a Cyt1 or Cyt2 cytoplasmic tail. All transgenic lines expressed CD46 protein in the brain. Newborn transgenic mice, in contrast to nontransgenic controls, were highly sensitive to intracerebral infection by the MV Edmonston strain. Signs of clinical illness (lack of mobility, tremors, and weight loss) appeared within 5 to 7 days after infection, followed by seizures, paralysis, and death of the infected animals. Virus replication was detected in neurons from infected mice, and virus was reproducibly isolated from transgenic brain tissue. MV-induced apoptosis observed in different brain regions preceded the death of infected animals. Similar results were obtained with mice expressing either a Cyt1 or Cyt2 cytoplasmic tail, demonstrating the ability of different isoforms of CD46 to function as MV receptors in vivo. In addition, maternally transferred immunity delayed death of offspring given a lethal dose of MV. These results document a novel CD46 transgenic murine model where MV neuronal infection is associated with the production of infectious virus, similarly to progressive infectious measles encephalitis seen in immunocompromised patients, and provide a new means to study pathogenesis of MV infection in the CNS.Measles virus (MV) infection is one of the leading causes of infant death in developing countries, and sporadic outbreaks of acute measles still occur in industrialized countries despite vaccination (52). This virus causes acute respiratory infection in children, which can be followed in certain cases by invasion of the central nervous system (CNS) and development of three different forms of measles encephalitis (27). Acute postinfectious encephalomyelitis occurs during or shortly after acute measles and is characterized by perivascular inflammation in the brain and demyelinization. Virus replication cannot be detected in the brains of affected patients, and this encephalitis seems to be associated with autoimmune pathogenesis. In contrast to acute encephalitis, subacute sclerosing panencephalitis (SSPE) presents a late complication of measles, with an incubation time of 1 to 10 years. It is based on the persistent MV infection of brain cells, where virus has been found to be only cell associated, presenting numerous mutations in its genome (10). This fatal disease occurs in the presence of a competent immune response and is followed by general destruction of the brain tissue, causing a progressive dementia, seizures, and ataxia. The third form of MV-induced CNS disease, progressive infectious encephalitis (also known as a measles inclusion body encephalitis) occurs in immunosuppressed patients 1 to 6 months following measles infection. Seizures, motor and...

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Distribution of measles virus in the central nervous system of HIV-seropositive children

Cited by 36 publications

References 26 publications

Canine Distemper Virus Uses both the Anterograde and the Hematogenous Pathway for Neuroinvasion

Canine Distemper Virus Uses both the Anterograde and the Hematogenous Pathway for Neuroinvasion

Wild-type measles virus infection of primary epithelial cells occurs via the basolateral surface without syncytium formation or release of infectious virus

Productive Measles Virus Brain Infection and Apoptosis in CD46 Transgenic Mice

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