Experimental Feline Herpesvirus Infection in the Pregnant Cat

Intravenous inoculation of pregnant cats with feline herpesvirus produced minimal illness but resulted in abortion, intrauterine fetal death and congenital fetal infection. Placental lesions included multiple infarcts in the placental labyrinth, thrombosis of maternal vessels in the endometrium and placenta, and multifocal necrosis of the giant-cell trophoblast and endometrial epithelium in the junctional zone of the placenta associated with eosinophilic intranuclear inclusion bodies. The virus was isolated from all the placentas and uteri but from none of the fetuses aborted 6-9 days after maternal intravenous inoculation. Viral antigen was demonstrated in the uterine vessels and in the junctional zone of the placenta at this time. On postinoculation day 26, viral antigen was demonstrated in the chorioallantoic membrane on the fetal side of the placenta and in the liver of a congenitally infected fetus. Although all 4 pregnant cats inoculated intranasally with feline herpesvirus aborted, neither virus, viral antigen nor significant lesions were detected in the uteri, placentas or fetuses. Abortion after intranasal inoculation was interpreted as a nonspecific reaction secondary to the severe, debilitating upper respiratory disease that occurred.     

Placental and fetal alterations due to Venezuelan equine encephalitis virus in rats.

Histopathological changes in the placentas, embryos, and fetuses of rats inoculated intraperitoneally with the virulent Guajira strain of Venezuelan equine encephalitis virus were studied by light microscopy and immunoperoxidase methods. Rats inoculated before day 15 of pregnancy showed necrosis and hemorrhages in the embryonic disks. Swelling of cytoplasm and nuclear pyknosis of cyto- and syncytotrophoblastic cells were noted as early as 2 days after inoculation. During weeks 1 and 2 of pregnancy, death of the embryos was always observed 3 to 4 days after Venezuelan equine encephalitis virus inoculation. Placental and fetal damage varied among the specimens. In rats 18 days pregnant and sacrificed 2 days after inoculation, there were some viable fetuses; the placentas showed inflammatory reactions in the mesometrial and decidual vessels. Other rats sacrificed at 3 to 4 days after inoculation showed large placental infarcts with fetal death. Viremia peaked during day 2 after inoculation. Immunoperoxidase stains demonstrated viral antigens present in the decidua, myometrium, and cyto- and syncytotrophoblastic cells. These experiments provide additional data regarding the pathogenesis and structural damage in the placental and fetal tissues caused by Venezuelan equine encephalitis virus.     

Coxsackievirus B infection in pregnant mice and transplacental infection of the fetus.

Direct instillation of coxsackievirus B1 into the gastrointestinal tracts of albino mice caused viremia in more than 85% of the animals within 1 day. In pregnant mice infected early in gestation (7 days), the geometric mean titer of virus in the blood was lower (P = 0.02) and the duration of viremia was shorter (P = 0.07) than in nonpregnant female mice, but infection of the heart, liver, and uterus did not differ on each of 5 days after infection. Although transplacental infection of the placenta or fetus or both occurred, the high spontaneous abortion rate (48%) obviated comparison of transplacental infection in these mice with mice infected later in gestation. Pregnant mice infected in the third trimester had significantly greater geometric mean titers of virus in the blood, heart, liver, and uterus, and infection persisted longer than in nonpregnant mice (P = 0.04). A very high geometric mean titer of virus was recovered from the uteri of these mice for 3 days after infection, whereas simultaneous geometric mean titers of virus in the placentas and fetuses were lower. In the majority of third trimester pregnant mice, virus was found in low titers in the fetuses at 2 and 3 days after maternal infection, and virus was not detected after day 3. We conclude that coxsackievirus B1 infection in late gestational pregnant mice is more severe than in mice at earlier gestational stages and in nonpregnant mice and that transplacental infection of the fetus occurs transiently during maternal infection. This model will prove useful in the study of perinatal enterovirus infection and in examination of the numerous factors that may influence outcome of infection of perinatally infected newborn infants.     

Experimental encephalomyocarditis virus infection in pregnant mice

The present study was carried out to clarify the mode of encephalomyocarditis (EMC) virus infection in pregnant mice. Pregnant BALB/c mice were intraperitoneally inoculated with the D variant of EMC virus (EMC-D) (5 x 10(2) PFU/mouse) on 11 days of gestation and killed at 1, 3, and 5 days post-inoculation (DPI). The virus titer (dam's serum, placenta, and fetus), histopathology (fetus, placenta, and uterus), distribution of viral RNA (fetus, placenta and uterus), and ultrastructure (fetal heart and placenta) were examined. No deaths occurred to fetuses at 1 DPI but almost all fetuses died at 5 DPI. The virus titers of dam's serum and placenta were elevated at 1 DPI, peaked at 3 DPI, and the former was not detected at 5 DPI. The virus titer of fetus was first elevated at 3 DPI and the level was lower than those of others. Histopathological changes and signals of viral RNAs detected by in situ hybridization (ISH) were observed in the spongiotrophoblast layer of placenta and in the fetal myocardium and liver at 3 DPI. The uterus was free from lesions and signals of viral RNA. Ultrastructural changes developed in trophoblast cells and giant cells in the spongiotrophoblast layer at and after 1 DPI and in fetal myocardial cells at 3 DPI. In the cytoplasm of trophoblast cells and giant cells, aggregations of virus-like particles 20-30 nm in diameter were observed in crystalline array. These results suggest that trophoblast cells and giant cells in the spongiotrophoblast layer are the main target of EMC virus in the placenta and that placental damage as well as the direct effect of virus to fetuses may be a cause of fetal death.     

Attenuated variants of eastern equine encephalomyelitis virus: pathomorphological, immunofluorescence and virological studies of infection in Syrian hamsters.

A virulent strain of eastern equine encephalomyelitis virus produced in hamsters a lethal infection with severe lesions of nerve cells predominatly in the anterior parts of the brain. Parenchyma necroses occurred in the liver and lymphoid organs. Infectious virus and viral antigen were found in all the organs examined with the greatest accumulation in the brain. Attenuated variants of the virus produced in most hamsters an inapparent infection. In some animals without clinical signs, focal inflammatory-dystrophic lesions were found in the central nervous system (CNS) and the liver, as were immunomorphological changes in the lymphoid tissue. In the latter infectious virus could be detected for 6 days after inoculation (p.i.), whereas in the brain only viral antigen could be found up to 14 days. At 3 and 6 months p.i., no persistence of attenuated virus in the brain and lymphoid tissues could be established by organ culture and co-cultivation methods. Nor was virus antigen detected. No pathomorphological changes or proliferative-hypertrophic astrocyte reaction were found.     

Monoclonal antibodies against maternal major histocompatibility complex class I molecules induce rapid abortion in mice.

PROBLEM: The role of antibodies against fetal or maternal antigens in maintaining or losing pregnancy is not clear. METHOD OF STUDY: Term-pregnant mice were injected with monoclonal antibodies against only fetal or fetal and maternal major histocompatibility complex class I molecules. The development of pregnancy was then followed. RESULTS: Antibodies against maternal, but not fetal, major histocompatibility complex class I molecules induced abortion in mice. The abortion occurred 6-8 hr after the administration of autoreactive antibodies. The abortion could only be induced after the formation of placenta. Antibodies against tumor necrosis factor-alpha could not prevent or postpone the abortion. Extensive bleeding has been detected in the placenta of aborting mice 3 hr after the administration of the antibodies. CONCLUSIONS: This study indicates that autoreactive antibodies present risk for pregnancy and that the damage leading to abortion induced by such antibodies most likely occurs at the maternal side of placenta.     

Kinetics and pathogenicity of oral infection by equine herpesvirus-9 in mice and suckling hamsters

The pathogenesis and kinetics of oral infection by equine herpesvirus (EHV)-9 were studied in mice and hamsters. After oral inoculation of 10(5) plaque-forming units (PFU) of virus, 1-week-old suckling hamsters showed varying severity of neurological disease from 72 hours post inoculation (hpi) and all of these animals had died by 96 hpi. Four-week-old ICR mice inoculated orally with 4 × 10(4)PFU of virus showed no clinical signs, but they developed erosive and ulcerative gastritis from 36 hpi. Varying degrees of encephalitis were seen in infected mice and hamsters, and the hamsters also developed myelitis by 96 hpi. Immunohistochemistry performed on whole body sections of suckling hamsters revealed the kinetics of spread of the virus to the central nervous system. EHV-9 antigen was detected initially in macrophages of the oral and lingual submucosa. At 36 hpi virus antigen was detected in the nerve fibres and pseudounipolar neurons of the trigeminal ganglion and at 96 hpi antigen was present in the myenteric plexuses of the intestine. Virus antigen was also detected in the liver, lungs and heart of affected animals. EHV-9 DNA was detected by polymerase chain reaction in the brain, blood and spinal cord of suckling hamsters at 36, 48 and 96 hpi. These findings show that EHV-9 may spread via the trigeminal nerve when mice and hamsters are inoculated orally with virus.     

Induction of cytochrome P450 isozymes by phenobarbital in pregnant rat and fetal livers and placenta

Cytochrome P450 (CYP) isozymes are important in metabolizing xenobiotics. They are found in extrahepatic tissues such as placenta as well as liver. Previously, we reported that CYP3A1 was detected in the cytoplasm of giant cells in the trophoblastic region of placenta of rats through pregnancy. In this study, we examined the changes in the expression of CYP proteins in the pregnant rat and fetal livers and placenta after treatment with phenobarbital (PB), one of the antiepileptic drugs which is well known to induce several phase I and phase II drug metabolizing enzymes in the liver. Namely, F344 pregnant rats were treated with PB (80 mg/kg, i.p.) from 13 days of gestation (DG) to 16 DG. All animals were sacrificed on 17 DG, and Western blot analysis and immunohistochemical staining on nine CYP proteins (CYP1A1, CYP2B1, CYP2C6, CYP2C12, CYP2D1, CYP2D4, CYP2E1, CYP3A1, and CYP4A1) and histological examination were done in the dam's liver, placenta, and the fetal liver. Western blot analysis revealed that CYP3A1 protein was significantly induced, CYP2B1 protein was detected, and CYP2D1 protein was significantly decreased in the dam's liver after PB-treatment. In placenta, only CYP3A1 was detected with no difference between control and PB-treated animals. The results of immunohistochemical staining corresponded closely to those of Western blot analysis in the dam's liver and placenta. In the fetal liver, CYP3A1 and CYP2C6 proteins were significantly induced after the PB-treatment, but their immunostainability was not prominent. The present results are considered useful as a basis for further investigation of drug metabolism in pregnant animals.     

Histologic, infectious, and molecular correlates of idiopathic spontaneous abortion and perinatal mortality.

The purpose of this study was to analyze the placental and neonatal tissues in fatal cases for a wide variety of infectious agents and cytokine expression. Placentas and corresponding neonatal tissues in 21 consecutive cases of idiopathic spontaneous abortion or perinatal death, before or within 2 days of birth, were tested for an infectious agent. The controls included 10 consecutive cases of fetal and placental tissues from therapeutic abortions, 5 placentas from unremarkable childbirths, and 11 placentas from cases of spontaneous abortion or perinatal death of known cause (ruptured uterus, placenta abruption, prolapsed cord). An intrauterine infection was noted in 16 of 21 (76%) of the placentas associated with neonatal mortality; in each case, the same infectious agent was found in the neonatal tissues, primarily the spleen. The most common infectious agent was enterovirus/coxsackie virus (10 cases); the histologic findings in the placenta were nonspecific. There was strong expression of TNF-alpha in the placenta and spleen of each of the cases of intrauterine infection and in none of the 26 controls. It is concluded that in utero infection and the associated cytokine up-regulation are responsible for many cases of unexplained fetal and neonatal loss.     

Effect of exogenous interferon and an interferon inducer on western equine encephalitis virus disease in a hamster model

Mice are used as models for western equine encephalitis virus (WEEV) infection, but high mortality is generally only seen with intracranial or intranasal challenge, while peripheral inoculation results in approximately 50% mortality and is not dose-dependent. Hamsters were therefore studied as a model for WEEV infection. Hamsters were highly sensitive to intraperitoneal (i.p.) infection with WEEV. Disease progression was rapid, and virus titers in serum, brain, liver, and kidney of infected hamsters peaked between 2 and 4 days post-virus inoculation (dpi). Foci of virus infection were detected in neurons of the cerebral cortex and midbrain. Pre-treatment i.p. with either interferon alfacon-1 (5 microg/kg/day) or with Ampligen (3.2 mg/kg/day) resulted in complete survival, reduced brain titers, and improved weight gain. This model of WEEV infection in hamsters appears to serve as a suitable model for the evaluation of potential therapeutic agents for the treatment of WEE disease.     

Epizootic congenital arthrogryposis-hydranencephaly syndrome in cattle: Isolation of Akabane virus from affected fetuses

Summary Previous serological studies strongly suggested Akabane virus to be the etiologic agent of epizootic abortion and congenital arthrogryposis-hydranencephaly in cattle, and this view was further corroborated in this study by the isolation of the virus from an aborted fetus in an epizootic of the disease and from a fetus extracted from a cow which was suggested by serologic tests to have a recent infection with the virus. The latter fetus had histological changes of encephalomyelitis and polymyositis, and specific antigens of Akabane virus was shown by the immunofluorescent technique in brain tissues as well as skeletal muscular tissues. The virus was recovered from various fetal tissues and fluids, and in relatively large amounts from brain, spinal cord, cerebral fluid, skeletal muscles and fetal placenta. The intracranial inoculation of suckling mice, 1–2 days of age, was the most sensitive system for Akabane virus isolation and Hm Lu-1, a continuous cell line from hamster lung, seemed almost as sensitive as suckling mice.With 1 Figure     

Infection of newborn and fetal hamsters induced by inoculation of Lu III parvovirus

Summary The Lu III parvovirus was adapted to the newborn hamster and produced a systemic infection with massive intestinal hemorrhage. Inoculation of pregnant hamsters lead to transplacental infection of the fetuses and abortion. Most fetal deaths were observed in animals inoculated on days 8 and 10 of gestation. Virus was recovered from dead fetuses, placentas, and viable fetuses. Histological lesions were found in the heart, liver, kidney and CNS of infected fetuses.     

Microscopical lesions and antigen distribution in bovine fetal tissues and placentae following experimental infection with bovine herpesvirus-1 during pregnancy

As part of a larger investigation, gross and histopathological examinations were carried out on six aborted and one non-viable calf born to heifers inoculated with bovine herpesvirus-1 (BHV-1) early in the third trimester of pregnancy. Antibody titres in sera collected from the dams confirmed seroconversion following inoculation. Samples of liver, lung, kidney, brain, heart, spleen, hepatic lymph node and placenta were subjected to histopathological examination. Immunohistochemistry for the detection of BHV-1 antigen was performed on liver and placenta from each calf, and on the full range of tissue from three of the six calves. Six dams aborted between 15 and 50 days post-inoculation (dpi) whilst one produced a live but non-viable calf at 51dpi. Consistent microscopical findings in tissues from the six aborted calves were multifocal coagulative necrosis in the liver and necrotic placentitis. The latter was characterized by villous necrosis, necrosis of vascular endothelium and infiltration of necrotic villi by mixed inflammatory cells. Other findings included multifocal necrosis in kidney, spleen and hepatic lymph node as well as haemorrhage in the lung and kidney. Immunohistochemistry confirmed the presence of BHV-1 antigen in association with these lesions and also revealed focal labelling of the endothelium of small blood vessels and surrounding glial processes in the brains of three calves. Virus isolation confirmed the presence of BHV-1 in the placentae from the six aborted calves and in pooled tissues of three of the fetuses. It is concluded that the pathogenesis of BHV-1 abortion involves infection of vascular endothelial cells in multiple tissues including placenta and brain. Furthermore, histopathological examination in suspected cases of BHV-1 abortion should include placenta as well as fetal viscera, and immunohistochemistry is a valuable tool for confirming a diagnosis of infection with the virus.     

Characterization of Persistent Modoc Viral Infections in Syrian Hamsters

Adult Syrian hamsters were readily infected by intranasal inoculation with Modoc virus. Viremias were detected 2 to 6 days after infection and peak viremia titers (10^6.2 plaque-forming units/ml of blood) occurred 4 days postinoculation. All infected animals developed neutralizing and hemagglutination-inhibiting antibodies by 7 days, and complement-fixing antibodies by 14 days postinoculation. High titers of antibodies persisted for at least 4 months. Modoc virus was recovered from throat swabs at 7 days postinoculation, but not at 14 days or later. Urine samples were positive for virus throughout a 12-week observation period. Isolation of virus from lungs and kidneys of one and three animals, respectively, at 151 to 221 days after inoculation confirmed chronic infection. Viral isolations were made only when organs were cultivated in vitro and were unsuccessful by tests on 10% homogenates of the organs. Horizontal viral transmission of virus by infected hamsters that were viruric was demonstrated in only 1 of 27 normal hamsters that were cocaged for 4 weeks under crowded conditions. General failure to obtain horizontal viral transmission may relate to rapid inactivation of virus in excreted urine. Vertical viral transmission was not demonstrated from five chronically infected female hamsters to their 34 offspring. However, if primary infection occurred during pregnancy, the progeny were either stillborn or died shortly after birth, and thus appeared to represent transplacental viral transmission.     

Roles of the surface layer proteins of Campylobacter fetus subsp. fetus in ovine abortion

The role of the surface (S)-layer proteins of Campylobacter fetus subsp. fetus has been investigated using an ovine model of abortion. Wild-type strain 23D induced abortion in up to 90% of pregnant ewes challenged subcutaneously. Isolates recovered from both dams and fetuses expressed S-layer proteins with variable molecular masses. The spontaneous S-layer-negative variant, strain 23B, neither colonized nor caused abortions in pregnant ewes. A series of isogenic sapA and recA mutants, derived from 23D, also were investigated in this model. A mutant (501 [sapA recA(+)]) caused abortion in one of five challenged animals and was recovered from the placenta of a second animal. Another mutant (502 [sapA recA]) with no S-layer protein expression caused no colonization or abortions in challenged animals but caused abortion when administered intraplacentally. Mutants 600(2) and 600(4), both recA, had fixed expression of 97- and 127-kDa S-layer proteins, respectively. Two of the six animals challenged with mutant 600(4) were colonized, but there were no abortions. As expected, all five strains recovered expressed a 127-kDa S-layer protein. In contrast, mutant 600(2) was recovered from the placentas of all five challenged animals and caused abortion in two. Unexpectedly, one of the 16 isolates expressed a 127-kDa rather than a 97-kDa S-layer protein. Thus, these studies indicate that S-layer proteins appear essential for colonization and/or translocation to the placenta but are not required to mediate fetal injury and that S-layer variation may occur in a recA strain.     

Taurine concentrations in fetal, neonatal and pregnant rats

The concentrations of taurine in the fetal and neonatal organs, and the maternal organs, plasma and urine of rats between the 15th day of gestation and the 21st day after birth were determined using an automatic amino acid analyzer. In the fetal liver and brain and in the placenta, the taurine concentration was the highest of all ninhydrin positive compounds. In the fetal liver and placenta, the concentrations of taurine increased significantly with the gestational days. Concentrations of taurine in the brain were much higher in the fetus and neonate than that in the adult. Moreover, the total amount of taurine per fetus increased markedly after the 15th day of gestation, and near term, reached almost the same amount as in the adult rat liver. In contrast to this, a significant decrease was observed in the taurine concentration in the maternal liver and muscle near term. The concentration of taurine in the urine of pregnant rats decreased near term, but in the plasma of pregnant rats the concentration of taurine did not change during pregnancy.     

Microarray analysis on Phase II drug metabolizing enzymes expression in pregnant rats after treatment with pregnenolone-16alpha-carbonitrile or phenobarbital

We previously reported the expression profiles of 9 cytochrome P450 isozymes (CYPs) proteins and those of 40 CYPs genes in pregnant rat's liver, placenta and fetal liver after treatment with pregnenolone-16alpha-carbonitrile (PCN) or phenobarbital (PB). This study was carried out focusing on the gene expression profiles of Phase II drug metabolizing enzymes, Glutathione S-transferase isozymes (GSTs) and UDP-glycosyltransferase isozymes (UDPGTs). Fischer 344 (F344) pregnant rats were daily treated intraperitoneally with 50 mg/kg of PCN or 80 mg/kg of PB from 13 to 16 days of gestation (DG). They were sacrificed on 17 DG, and microarray analysis using Affymetrix Rat Expression Array 230 A was performed. Among 16 GSTs genes examined in this study, 7 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 8 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. On the other hand, among 11 UDPGTs genes examined, 5 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 5 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. There were no significant changes in the placenta of all groups. This is the first report of the gene expression profiles of Phase II drug metabolizing enzymes in pregnant rat and fetal livers and placenta after treatment with typical inducers of drug metabolizing enzymes.     

Opsonization of alphaviruses in hamsters

Immune elimination of alphaviruses in immunized hamsters appears to involve formation of virus/antibody aggregates which are subsequently cleared from the circulation by cells of the reticuloendothelial system (RES). Virulent strains of Venezuelan (VEE) and Western equine encephalitis (WEE) viruses which were cleared slowly from the circulation of nonimmune hamsters, were cleared rapidly when inoculated into the blood of immunized hamsters. Likewise, when these viruses were mixed with specific hamster immune serum prior to inoculation, they were efficiently cleared from the circulation of nonimmune hamsters. Virus, mixed with specific immune serum, or inoculated into immunized hamsters, formed virus/antibody aggregates, as demonstrated by density gradient centrifugation, filtration through polycarbonate membranes, precipitation with Staphylococcus protein A, and electron microscopy. Cleared virus was concentrated primarily in liver and spleen, as confirmed by autoradiography. Immune clearance of virulent VEE was demonstrable within 5 to 6 days following immunization of hamsters with live attenuated VEE vaccine, strain TC-83. In these hamsters, a close association was established between formation of virus/antibody aggregates, rapid clearance, and survival of challenged hamsters. Adsorption of virus to hamster macrophages in culture was enhanced by immune serum in the presence of complement. These results are compatible with the hypothesis that immune clearance of virus in the intact hamster involves a complement-dependent interaction of virus/antibody complexes with cells which possess Fc and complement receptors. The clearance of immune complexes by the RES serves to amplify the protective effect of neutralizing antibody alone.     

Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model

Mammalian pregnancy is thought to be a state of immunological tolerance. The mechanisms underlying this phenomenon are still poorly understood. Here, we determined whether an inappropriate function of T regulatory (Treg) cells is involved in the pathogenesis of spontaneous abortion. We evaluated spleen and decidual lymphocytes from CBA/J mice undergoing immunological abortion (DBA/2J-mated) or having normal pregnancy (BALB/c-mated) on day 14 of gestation for ex vivo cytokine production after PMA or paternal antigen (alloantigen) stimulation. Treg activity was characterized by quantifying CD4(+)CD25(+) cells, foxp3 expression, and interleukin-10 secretion. Decidual lymphocytes from abortion CBA/J mice contained a significantly higher frequency of interferon-gamma-producing T cells specific for paternal antigens compared to those from normal pregnancy (7.8% versus 2.7%, P < 0.05). Compared to virgin CBA/J females, normal pregnant mice showed strongly elevated numbers of CD4(+)CD25(+) and interleukin-10(+) Treg cells in the thymus whereas significantly lower frequencies of Treg cells were observed in abortion mice. Very interestingly, CD4(+)CD25(+) Treg cells from normal pregnant and nonpregnant CBA/J mice could inhibit both proliferation and interferon-gamma secretion of lymphocytes from abortion mice in vitro whereas in vivo prevention of fetal rejection could only be achieved after adoptive transfer of Treg cells from normal pregnant mice. Our data suggest that pregnancy-induced Treg cells play a vital role in maternal tolerance to the allogeneic fetus.     

Experimental measles infection in rodents

The sensitivity of newborn hamsters to inoculation with the vaccine L-16 strain of measles virus and the Lec strain isolated from a patient with subacute sclerosing panencephalitis as well as the possibility of persistence of these viruses in the animals were studied. Intracerebral inoculation of the L-15 strain was shown to produce in hamsters acute meningoencephalitis leading to death in 85%-100% of cases. Over 30 days after inoculation, the infectious virus, the virus-specific antigen and virus genome were found in the brain. In the brains of the sick animals, all the structural proteins of measles virus with the exception of hemagglutinin were expressed. After inoculation with the Lec strain, the clinical signs of the disease were less manifest, and mortality was 40%. The infectious virus could be detected in the brain up to 20 days postinoculation, the genome, up to 31 days. All the structural proteins of measles virus were expressed in the brains of the inoculated animals. No persistence of L-16 and Lec strains of measles virus could be demonstrated at langer intervals after inoculation (90-180 days) in the brains of hamsters.