Lymphocytic Choriomeningitis Virus: An Unrecognized Teratogenic Pathogen

Barton, Leslie L.; Peters, C. J.; Ksiazek, T. G.

doi:10.3201/eid0104.950410

Cited by 76 publications

(43 citation statements)

References 10 publications

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“…The higher seropositivity rate in females is of concern since LCMV is also a teratogenic pathogen. 13 Barton and others 13 described three infants with congenital LCMV and summarized data on an additional three infected infants. All five for whom detailed information was available had nonobstructive hydrocephalus with periventricular calcifications, chorioretinitis, and psychomotor retardation.…”

Section: Discussionmentioning

confidence: 99%

Seroprevalence of lymphocytic choriomeningitis virus in Nova Scotia.

Marrie¹,

Saron²

1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. An ELISA system was used to determine the rate of seropositivity to lymphocytic choriomeningitis virus (LCMV) among a random sample of 505 Nova Scotians. Twenty (4%) were positive. Complete questionnaire data were available on all 20 seropositive subjects and on 449 seronegative subjects. Seventeen (85%) of the seropositive subjects were females (P ϭ 0.03). It is concluded that infection with LCMV is present in Nova Scotia and females are more likely to be infected than males.Lymphocytic choriomeningitis virus (LCMV) is an arenavirus that causes meningitis 1 and a flu-like illness characterized by malaise, myalgia, retroorbital headache, and photophobia. 2 A variety of other manifestations including testicular pain, parotid pain, and rash may occur. 2 Outbreaks of LCMV infection have followed exposure to infected mice and hamsters raised in research laboratories. 3, 4 An investigation by the New York State Department of Health revealed that 55 of 60 patients with LCMV infection had pet hamsters and four others were employees of hamster wholesalers. 5 It has also been shown that the house mouse, Mus musculus, is commonly infected with this virus. 6 Childs and others 6 found that 9% of 484 mice trapped in urban sites in Baltimore were seropositive for LCMV. It is thus likely that infection with LCMV is common among a variety of rodents. We have not recognized cases of LCMV infection in Nova Scotia. A study of a random sample of the Nova Scotian population was used to determine the rate of LCMV infection in this province. POPULATION, MATERIALS, AND METHODSStudy population. The names of 6,000 persons 16-70 years of age were randomly selected from a comprehensive listing of all residents of Nova Scotia maintained on the Provincial Medical Services Insurance computer. Contact with 5,915 was made by mail (85 had incomplete mailing addresses), of whom 808 (14%) responded, and 590 (10%) agreed to participate. These individuals returned their signed informed consent and completed questionnaire, and a baseline blood sample was collected by their family physician. The ages and geographic distribution of the respondents did not differ from the population from which they were selected. Follow-up of these individuals was made by mail between 1988 and 1991, one and two years after enrollment. Each year, subjects were again asked to complete a questionnaire and provide a blood sample. Five hundred five subjects were tested in this study. Four hundred sixty-nine had complete questionnaire data. This study was approved by the Nova Scotia Department of Health and by the Research Review Committee of Dalhousie University.Determination of the presence of antibodies to LCMV. Preparation of LCMV antigen. The LCMV strain Arm/53b was grown in BHK-21 cells. All supernatants were purified by sucrose density gradient centrifugation. 7 Uninoculated cells treated in the same fashion as inoculated cells were used as negative control antigen. Nunc polysorb (Polylabo Paul Block et Cie, Strasbourg, France) ELISA plates were used; half of...

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Section: Discussionmentioning

confidence: 99%

Seroprevalence of lymphocytic choriomeningitis virus in Nova Scotia.

Marrie¹,

Saron²

1998

The American Journal of Tropical Medicine and Hygiene

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“…Microencephaly, chorioretinitis, hydrocephalus, and periventricular calcifications are frequently noted features (6,18,46). These neuropathological changes lead to mental retardation, impaired coordination, spasticity, blindness, and epilepsy in children with congenital LCMV infection (5,7,46). The pathogenic mechanisms underlying LCMV-induced injury of the fetal human brain are unknown.…”

mentioning

confidence: 99%

Critical Role for Glial Cells in the Propagation and Spread of Lymphocytic Choriomeningitis Virus in the Developing Rat Brain

Bonthius

Mahoney²,

Buchmeier

et al. 2002

J Virol

103

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Inoculation of the neonatal rat with lymphocytic choriomeningitis virus (LCMV) results in the selectiveLymphocytic choriomeningitis virus (LCMV) is a rodentborne arenavirus and a prevalent human pathogen (11,12,29). Infection of the postnatal human with LCMV typically results in only a mild febrile illness, from which the patient recovers fully. In contrast, when the infection occurs during pregnancy, the fetal brain can be severely damaged. Microencephaly, chorioretinitis, hydrocephalus, and periventricular calcifications are frequently noted features (6,18,46). These neuropathological changes lead to mental retardation, impaired coordination, spasticity, blindness, and epilepsy in children with congenital LCMV infection (5,7,46). The pathogenic mechanisms underlying LCMV-induced injury of the fetal human brain are unknown.Although the human fetal brain is vulnerable throughout gestation to the teratogenic effects of LCMV, many of the case reports of congenital LCMV infection describe infants who were infected during the third or late second trimester (21,23,42,46). This is a period of rapid brain growth, referred to as the brain growth spurt (17), and is a time when many neuroteratogens exert adverse effects (9,15). While all mammalian species have a brain growth spurt, the timing of this event, relative to birth, varies among the species. Relative to the human brain, the rat brain is immature at birth, and the brain growth spurt in the rat occurs during the first two postnatal weeks (16,17). Therefore, an accurate model of human mid-or late-gestation LCMV infection requires infection of the rat during early postnatal life.The neonatal rat inoculated with LCMV serves as an excellent model system for human congenital LCMV infection. LCMV infection in suckling rats induces microencephaly, retinitis, and the selective destruction of several brain regions (32,34,38). These neuropathologic changes manifest as permanent abnormalities of movement, coordination, vision, and behavior, reminiscent of human congenital LCMV infection (14,30,31).In the neonatal rat brain, inoculation of LCMV induces a distinct pattern of infection in which specific neuronal populations are consistently infected, while others are spared (13,34). This selectivity of infection likely underlies the focal pathological changes which follow. However, the susceptible neuronal populations are widely separated, and the pathway by which LCMV reaches these neurons has not been identified. Elucidation of this pathway is of substantial importance, not only for a better understanding of LCMV biology and teratogenesis, but because the cells utilized by LCMV in its sequential spread are sites to which therapeutic agents could be targeted to block the infection.One goal of this study was to examine the sequential migration of LCMV in the developing brain to identify the pathway by which LCMV reaches susceptible neurons. The results demonstrate that glial cells are the initial target cells of LCMV within the brain parenchyma and that LCMV spreads across the ...

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“…Similarly, in South America, Junin virus, machupo virus, Guanarito virus, and Sabia virus have emerged as causative agents of severe hemorrhagic fever disease (Peters, 2002). moreover, increasing evidence indicates that LCmV is a neglected human pathogen of clinical significance in congenital infections (Barton and mets, 1999;Barton et al, 2002;Barton et al, 1995;mets et al, 2000), and also represents a serious problem to immunosuppressed individuals (Fischer et al, 2006;Palacios et al, 2008). Thus far, licensed vaccines against Lassa virus or LCmV are not available, and current antiarenavirus therapy is limited to the use of the nucleoside analog ribavirin, which is only partially effective and can cause significant side effects.…”

Section: Interferons and Arenavirusesmentioning

confidence: 99%