A non-productive subacute sclerosing panencephalitis (SSPE) virus of human and ferret

Summary A non-productive syncytiogenic measles virus isolated from the brain of an SSPE patients was grown on Vero cells. The ultrastructure of the infected syncytia was studied by electron microscopic and immunoperoxidase techniques. It was compared with the isolate of the virus after passage in ferrets, the Edmonston strain of wild measles virus and the Halle productive strain of SSPE, all on Vero cells.The immunoperoxidase labeling of the cell membranes of the Edmonston measles virus infected cells was very heavy and uniform. In contrast, the labeling of the non-productive SSPE infected cells was clearly discontinuous. In the latter, there was a preponderance of intranuclear over cytoplasmic nucleocapsid formation, whereas cytoplasmic nucleocapsids were prevalent in the virion-producing strains.Many similarities between Vero cells infected with the wild measles virus and the Halle strain of SSPE were observed, although differences between this SSPE strain and strains reported by others were noted.     

Functional analyses of natural killer cells in macaques infected with neurovirulent simian immunodeficiency virus

Clearance of HIV and SIV from the peripheral blood by the cellular immune system lessens the viral burden in infected individuals and may have an impact on virus infection of the CNS and the development of CNS lesions. However, the role of immune responses in preventing or limiting CNS infection has not been clearly defined. We investigated the role of natural killer cells in the outcome of SIV infection of macaques as a model for humans with AIDS and HIV encephalitis. In our study, six pig-tailed macaques were infected with the neurovirulent virus, SIV/17E-Fr, and the immunosuppressive virus, SIV/ DeltaB670, in a model system that causes rapid progression to AIDS and a high frequency of CNS lesions. NK lytic activity in each macaque was monitored longitudinally. In addition, we enumerated NK cells and tested macaque PBMC for the ability to lyse SIV-infected target cells. We found that there was a significant inverse correlation (P=0.02) between the robustness of NK response and the development of CNS lesions. Animals lacking strong NK cell responses developed more severe CNS lesions than those with robust NK responses did. Furthermore, pre-infection levels of NK activity were predictive of CNS lesion severity. The macaque with the most robust pre-infection NK activity developed no CNS lesions. In these infected macaques, NK activity was shown to be directed against SIV-infected cells. We extended these in vivo findings to delineate precisely which cell type was mediating this SIV-directed lysis. We used both macaque and human cells to demonstrate that the population that mediated anti-SIV and anti-HIV cytolytic effects was NK cells. Furthermore, we showed that this anti-SIV and anti-HIV cytolytic effect was directed at the envelope protein and not gag proteins. Thus, NK cells have the capacity to recognize and lyse cells expressing SIV and HIV antigens. These data support a role for NK cells in the modulation of CNS disease.     

CD8+-dependent CNS demyelination following ocular infection of mice with a recombinant HSV-1 expressing murine IL-2

Demyelinating diseases comprise a spectrum of immunopathologic syndromes in which myelin, the fatty covering of nerve cell fibers in the brain and spinal cord, is destroyed. In this study, we have shown for the first time that ocular infection of BALB/c mice with a recombinant herpes simplex virus type 1 (HSV-1) expressing IL-2 (HSV-IL-2) results in CNS demyelination as determined by light microscopy and EM. The demyelinated lesions involve periventricular white matter, brain stem, and spinal cord white matter. Demyelination was detected in the CNS of infected mice up to 75 days (the longest time point tested) post HSV-IL-2 infection. In contrast, mice infected with HSV-IFN-gamma or HSV-IL-4, which are identical to HSV-IL-2 but express IFN-gamma or IL-4 instead of IL-2, did not exhibit demyelination. Control mice infected with wild-type HSV-1 or parental virus also remained free of these symptoms. During early times (days 3-7), post-infection with HSV-IL-2 virus, a T(H)1 + T(H)2 pattern of cytokines was produced by lymphocytes of infected mice while mice infected with HSV-IFN-gamma or control viruses produced a T(H)1 pattern of cytokine. By day 21 post-infection, all infected groups exhibited a T(H)1 pattern of response. Immunohistochemistry and FACS analyses of infiltrates in the brains and spinal cords of HSV-IL-2-infected mice showed elevations in CD4+ and CD8+ T cells and macrophages. However, T cell depletion studies suggest that only central memory CD8+ T cells are directly involved in the demyelination process, with macrophages being involved through a bystander effect.     

Cell-specific posttranslational events affect functional expression at the plasma membrane but not tetrodotoxin sensitivity of the rat brain IIA sodium channel alpha-subunit expressed in mammalian cells.

The rat brain IIA Na+ channel alpha-subunit was expressed and studied in mammalian cells. Cells were infected with a recombinant vaccinia virus (VV) carrying the bacteriophage T7 RNA polymerase gene and were transfected with cDNA encoding the IIA Na+ channel alpha-subunit under control of a T7 promoter. Whole-cell patch-clamp recording showed that functional IIA channels were expressed efficiently (approximately 10 channels/microns2 in approximately 60% of cells) in Chinese hamster ovary (CHO) cells and in neonatal rat ventricular myocytes but were expressed poorly in undifferentiated BC3H1 cells and failed to express in Ltk- cells. However, voltage-dependent Drosophila Shaker H4 K+ channels and Escherichia coli beta-galactosidase were expressed efficiently in all four cell types with VV vectors. Because RNA synthesis probably occurs without major differences in the cytoplasm of all infected cell types under the control of the T7 promoter and T7 polymerase, we conclude that cell type-specific expression of the Na+ channel probably reflects differences at posttranslational steps. The gating properties of the IIA Na+ currents expressed in cardiac myocytes differed from those expressed in CHO cells; most noticeably, the IIA Na+ currents displayed more rapid macroscopic inactivation when expressed in cardiac myocytes. These differences also suggest cell-specific posttranslational modifications. IIA channels were blocked by approximately 90% by 90 nM TTX when expressed either in CHO cells or in cardiac myocytes; the latter also continued to display endogenous TTX-resistant Na+ currents. Therefore, the TTX binding site of the channel is not affected by cell-specific modifications and is encoded by the primary amino acid sequence.     

Cell activation and differentiation/Animal models (2)/Virus-host interactions

Two sibling viruses, Fr/V and Fr/B, of the subacute sclerosing panencephalitis (SSPE) virus Osaka-2 strain were isolated from a small biopsy specimen of the brain of an SSPE patient by cocultivation with two different cell lines, Vero and B95a cells, respectively. These two sibling viruses differ from each other in their molecular mechanisms of defective M protein expression. In this study, we found that the Fr/B virus could scarcely form syncytium foci on Vero cells, although the Fr/V virus could do so on both Vero and B95a cells, showing a similar relation of cell tropism between recent field isolates and laboratory strains of the measles virus. Severe neurovirulence of both Fr/V and Fr/B viruses was observed in hamsters inoculated intracerebrally with less than 100 PFU, in contrast to the negative neurological and pathological findings in hamsters inoculated even with more than 10(5) PFU of their possible progenitor measles virus. Comparative sequence analysis of inoculated viruses and reisolated viruses from diseased hamster brains showed few variations at a region containing the P-M gene junction, indicating that the inoculated viruses propagated in the brains and induced neurovirulence. All these results suggest that SSPE virus isolated with a lymphoid cell line is similar in neuropathogenicity to that isolated with a nonlymphoid cell lines, irrespective of differences in the molecular mechanism of M protein defectiveness.     

Electron-microscopic appearance of the DA virus, a demyelinating murine virus.

The DA virus is a neurotropic murine virus which can induce acute encephalomyelitis in suckling mice and a chronic myelopathy in weanlings. The agent has been attenuated by serial passage in baby hamster kidney (BHK-21) cells. When attenuated virus is inoculated in 8-week-old C3HeJ mice a myelopathy of delayed onset with prominent demyelination of lateral and anterior columns occurs. The DA virus is believed to be related to the Theiler murine encephalomyelitis (TME) viruses because of the similar clinical and pathological conditions which it causes, and because neutralization tests indicate shared antigens between it and GD7, a TME virus. This paper reports electron-microscopic studies of BHK-21 cells infected with DA virus. The cells were prepared 24 and 48 hr after inoculation. Cytopathic effects were observed and infected cells contained plaques consisting of numerous 25 nm virus particles in crystalline array. The virions were exclusively intracytoplasmic and were morphologically indistinguishable from human poliomyelitis virus. These observations appear to establish DA as a picorna virus, related to the TME virus group. The chronic myelopathy caused by DA may prove relevant to chronic demyelinative myelopathies in man, such as multiple sclerosis, and also to amyotrophic lateral sclerosis.     

Human immunodeficiency virus infection inhibits granulocyte-macrophage colony-stimulating factor-induced microglial proliferation

It is well known that infection by the human immunodeficiency virus (HIV) dysregulates cell physiology, but little information is available on the consequences of HIV infection in primary macrophages and microglia. The authors examined the relationship between cell proliferation and HIV infection in primary cultures of microglia and in human central nervous system (CNS). In cultures infected with HIV (ADA and BaL), granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated cell proliferation was reduced in productively infected (p24+) cells as compared to p24- cells. The reduction was observed with both Ki67 and BrdU labeling, suggesting a G1/S block. The reduction was insignificant when microglia were infected with a Vpr- mutant virus. In human CNS, proliferating (Ki67+) cells were rare but were increased in the HIV+ and HIV encephalitis (HIVE) groups compared to the HIV- group. A positive correlation between GM-CSF immunoreactivity and Ki67 counts, implicating GM-CSF as a growth factor in human CNS was found. The relationship between total macrophage (CD68+) proliferation and infected macrophage (p24+) proliferation was assessed in HIVE by double labeling. Whereas 1.2% of total CD68+ cells were Ki67+, only 0.5% of HIV p24+ cells were Ki67+ (P < .05). Furthermore, staining for CD45RB (as opposed to CD68) facilitated the identification of Ki67+ microglia, indicating that CD68 could underestimate proliferating microglia. The authors conclude that although there is increased expression of GM-CSF and increased cell proliferation in the CNS of HIV-seropositive individuals, cell proliferation in the productively infected population is actually suppressed. These data suggest that there might be a viral gain in the suppressed host cell proliferation.     

CNS-derived CCL21 is both sufficient to drive homeostatic CD4+ T cell proliferation and necessary for efficient CD4+ T cell migration into the CNS parenchyma following Toxoplasma gondii infection

Injury, infection and autoimmune triggers increase CNS expression of the chemokine CCL21. Outside the CNS, CCL21 contributes to chronic inflammatory disease and autoimmunity by three mechanisms: recruitment of lymphocytes into injured or infected tissues, organization of inflammatory infiltrates into lymphoid-like structures and promotion of homeostatic CD4+ T-cell proliferation. To test if CCL21 plays the same role in CNS inflammation, we generated transgenic mice with astrocyte-driven expression of CCL21 (GFAP-CCL21 mice). Astrocyte-produced CCL21 was bioavailable and sufficient to support homeostatic CD4+ T-cell proliferation in cervical lymph nodes even in the absence of endogenous CCL19/CCL21. However, lymphocytes and glial-activation were not detected in the brains of uninfected GFAP-CCL21 mice, although CCL21 levels in GFAP-CCL21 brains were higher than levels expressed in inflamed Toxoplasma-infected non-transgenic brains. Following Toxoplasma infection, T-cell extravasation into submeningeal, perivascular and ventricular sites of infected CNS was not CCL21-dependent, occurring even in CCL19/CCL21-deficient mice. However, migration of extravasated CD4+, but not CD8+ T cells from extra-parenchymal CNS sites into the CNS parenchyma was CCL21-dependent. CD4+ T cells preferentially accumulated at perivascular, submeningeal and ventricular spaces in infected CCL21/CCL19-deficient mice. By contrast, greater numbers of CD4+ T cells infiltrated the parenchyma of infected GFAP-CCL21 mice than in wild-type or CCL19/CCL21-deficient mice. Together these data indicate that CCL21 expression within the CNS has the potential to contribute to T cell-mediated CNS pathology via: (a) homeostatic priming of CD4+ T-lymphocytes outside the CNS and (b) by facilitating CD4+ T-cell migration into parenchymal sites following pathogenic insults to the CNS.     

FURTHER ULTRASTRUCTURAL OBSERVATIONS OF VIRUS MORPHOGENESIS AND MYELIN PATHOLOGY IN JHM VIRUS ENCEPHALOMYELITIS

Groups of 3, 17, and 28-day-old Swiss mice were inoculated intracerebrally with JHM virus, the neurotropic strain of mouse hepatitis virus (MHV), and studied serially by virologic and morphologic techniques. Beginning 2--5 days post-inoculation, all groups of infected mice developed CNS lesions which were destructive in the 3-day-old group and demyelinative in the 17 and 28-day-old animals. Infectious virus could be isolated from the brain, spinal cord, and liver. Electron microscopy demonstrated the virus to be pantropic in the CNS with virions occurring within ependymal cells, astrocytes, neurons, oligodendrocytes, endothelial cells, and cell of haematogenous origin. Giant cell formation was a constant feature. In regions of demyelination, oligodendrocytes exhibited a propensity to proliferative aberrant membrane. Myelin degradation was accompanied by membrane vesiculation and by the stripping action of macrophages. The lesions were not due to CNS elements in the inoculum since in animals inoculated with normal CNS suspensions from appropriate age groups failed to show lesions. The morphogenesis of JHM virions was followed ultrastructurally as was the formation of syncytia in the different cell types. In addition to delineating virus morphogenesis and myelin pathology, the results underscore the pantropic nature of JHM virus in the CNS, the synstemic nature of the infection, and that oligodendrocytes were the principal targets.     

Astrocytes and Schwann cells are virus-host cells in the nervous system of rats with Borna disease

Borna disease virus (BDV) replicates only in cells in the central (CNS) and peripheral (PNS) nervous system in adult rats. Infection of the nervous system is associated with a transient, intense mononuclear meningoencephalitis and immunemediated loss of BDV-infected neurons. The identification of BDV antigen in neurons and the accompanying immunologically-specific lysis of these cells led to the prediction that the CNS would be virus-free after the animal had recovered from encephalitis. However, BDV infectivity and antigen persist for the lifetime of the animal. It appeared, therefore, that other neural cells might be hosts for viral replication and provide a reservoir for the virus. Morphological criteria were used to identify astrocytes and Schwann cells which expressed BDV antigens in vivo. Borna disease virus (BDV) infected astrocytes were identified by double labeling tissue sections with combined cell-specific and BDV-specific antibodies in an avidin-biotin immunocytochemical assay. Examination of serial I micrometer-thick cryosections of hippocampus and sciatic nerve preparations revealed several cells that expressed both glial and BDV antigens. Infectious virus was recovered from cultures of Schwann cells from infected rats. Borna disease virus-infected glial elements persisted beyond the period of inflammation and massive neuronal destruction, and represented a major class of infected cells during chronic disease.     

Transplantation of glial-committed progenitor cells into a viral model of multiple sclerosis induces remyelination in the absence of an attenuated inflammatory response

Transplantation of remyelination-competent cells represents a promising strategy for the treatment of demyelinating diseases. As the environment dictates the success or failure of remyelination, it is critical to understand the role that the immune system plays in transplant-mediated remyelination. In this study, we evaluated the severity of neuroinflammation following transplantation of glial-committed progenitor cells into the spinal cords of mice chronically infected with mouse hepatitis virus (MHV), a model in which T cells and macrophages are critical in amplifying the severity of demyelination. Transplantation was performed following viral persistence in which inflammation and demyelination are established and clinical disease is evident. Mice were sacrificed 10 and 21 days following progenitor cell transplantation and the effect on neuroinflammation evaluated. Treatment did not alter accumulation of T cells or macrophages within the CNS as compared to control mice. Moreover, progenitor cell implantation did not affect local cytokine/chemokine gene expression in the CNS. Finally, remyelination associated with transplantation did not result in an imbalance of T(H)1-associated cytokine production by virus-specific T cells. These studies demonstrate that progenitor cell-mediated remyelination is not the result of modulating the composition of the cellular infiltrate nor cytokine expression by virus-specific T cells and suggest that remyelination may not depend on amelioration of the inflammatory response or alteration of cytokine secretion by virus-specific T cells.     

Virulent and attenuated canine distemper virus infects multiple dog brain cell types in vitro.

Canine Distemper Virus (CDV) produces an encephalitis in dogs that varies with viral strain. We have studied the cell tropisms of two virulent strains (CDV-SH and CDV A75-17) and an attenuated strain, Rockborn (CDV-RO), in cultured canine brain cells. Infected cell types were identified by double immunofluorescent labeling of specific cell markers and viral antigens. All viral strains studied produced infection in astrocytes, fibroblasts, and macrophages. Neurons were not infected by CDV A75-17 but were rapidly infected by CDV-SH and CDV-RO. Multipolar oligodendrocytes were very rarely infected by any of the virus strains. In contrast, a morphologically distinct subset of bipolar oligodendrocytes were commonly infected by CDV-SH and CDV-RO. The kinetics of infection in the astrocytes, oligodendrocytes, neurons, and macrophages varied between strains. Both CDV-SH and CDV-RO rapidly infected bipolar oligodendrocytes, astrocytes, neurons, and macrophages by 14 days post infection while infection by CDV A75-17 was delayed until after 28-35 days post infection. The differences in the growth kinetics and cell tropisms for some brain cells, exhibited by the three viral strains examined in this in vitro study, may relate to the different CNS symptoms that these strains produce in vivo.     

HSV (Type 1) infection of the trigeminal complex

Following corneal inoculation with herpes simplex virus (Type 1) (HSV), virus spreads to the CNS by axonal transport in the central branches of trigeminal ganglion cell neurons. Although this mode of viral entry to the CNS is rare for humans, it appears to be the principal route of entry into the CNS in animal models of herpetic corneal disease. In this study, the corneas of BALB/c mice were unilaterally inoculated with HSV, and the distribution of HSV-immunoreactive label was studied to identify the central branches of the axons of infected trigeminal ganglion cells. Virus was first noted in the brainstem trigeminal complex 4 days after corneal inoculation, when HSV-labeled afferents were found throughout the course of the descending tract of V as well as in interstitial neurons in the tract. By 5 days labeled neurons were also found not only in the n. caudalis and portions of the n. interpolaris of the trigeminal complex but also in laminae I–IV of the dorsal horn of the upper cervical levels of the spinal cord. No immunoreactivity was seen in other regions of the complex, including the n. oralis or the main sensory n. of V. By 6 days, however, the infection had spread to the main sensory division of V.     

Antibody in SSPE serum and brain IgG against measles virus smooth nucleocapsids detected by immunoelectron microscopy

Summary SSPE patients characteristically have high complement-fixing (CF) and neutralizing (N) antibody titers against measles virus in their sera, CSF, and brain. However, using SSPE patients' sera, the immunoperoxidase (IP) labeling of smooth nucleocapsids in SSPE or measles virus infected Vero cells or measles virions has not been achieved using conventional EM fixatives. Using the periodate-lysine-paraformaldehyde (PLP) fixative developed by McLean and Nakane (1974), and the indirect IP technique, antibodies against smooth nucleocapsids in SSPE and measles virus infected Vero cell cultures have been detected in serum from SSPE patients and normal individuals with high measles antibody titers.     

HIV-1 neuroimmunity in the era of antiretroviral therapy

Human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) can affect up to 50% of infected people during the disease course. While antiretroviral therapies have substantively increased the quality of life and reduced HIV-1-associated dementia, less severe minor cognitive and motor deficits continue. Trafficking of HIV-1 into the central nervous system (CNS), peripheral immune activation, dysregulated glial immunity, and diminished homeostatic responses are the disease-linked pathobiologic events. Monocyte–macrophage passage into the CNS remains an underlying force for disease severity. Monocyte phenotypes may change at an early stage of cell maturation and immune activation of hematopoietic stem cells. Activated monocytes are pulled into the brain in response to chemokines made as a result of glial inflammatory processes, which in turn, cause secondary functional deficits in neurons. Current therapeutic approaches are focused on adjunctive and brain-penetrating antiretroviral therapies. These may attenuate virus-associated neuroinflammatory activities thereby decreasing the severity and frequency of HAND.     

Microglia-mediated neuroinflammation is an amplifier of virus-induced neuropathology

Microglia, the major resident immune cells in the central nervous system (CNS) are considered as the key cellular mediators of neuroinflammatory processes. In the past few years, microglial research has become a main focus in cellular neuroimmunology and neuroinflammation. Chronic/remitting neurological disease such as multiple sclerosis (MS) has long been considered an inflammatory autoimmune disease with the infiltration of peripheral myelin-specific T cells into the CNS. With the rapid advancement in the field of microglia and astrocytic neurobiology, the term neuroinflammation progressively started to denote chronic CNS cell-specific inflammation in MS. The direct glial responses in MS are different from conventional peripheral immune responses. This review attempts to summarize current findings of neuroinflammatory responses within the CNS by direct infection of neural cells by mouse hepatitis virus (MHV) and the mechanisms by which glial cell responses ultimately contribute to the neuropathology on demyelination. Microglia can be persistently infected by MHV. Microglial activation and phagocytosis are recognized to be critically important in the pathogenesis of demyelination. Emerging evidence for the pathogenic role of microglia and the activation of inflammatory pathways in these cells in MHV infection supports the concept that microglia induced neuroinflammation is an amplifier of virus-induced neuropathology.     

Multiple neural cell types are infected in vitro by border disease virus

Border disease (BD) of sheep results from a congenitally acquired nonarbotogavirus infection which causes a highly selective central nervous system (CNS) pathological lesion consisting of diffuse decreased myelination without inflammation or neuronal destruction. Thus, a selective disruption of oligodendroglial function appears to occur. In order to investigate the in vitro cell tropism of BD virus, primary cultures derived from fetal and adult ovine CNS and peripheral nervous system were inoculated with BD virus. Infected cell types were determined by dual immunofluorescent labeling for viral and cell type specific antigens. Infection of all the major cell types represented in these cultures, including oligodendrocytes, astrocytes, fibroblasts, dorsal root ganglion neurons and Schwann cells was found. Oligodendrocytes were only infected earlier and appeared to remain infected longer than astrocytes and fibroblasts. Infectious virus was produced by all cultures and continued to be produced even after the disappearance of nearly all immunocytochemically detectable viral antigen within cells. These studies suggest that the selective dysfunction of the oligodendrocyte in BD is not based on a selective viral tropism.     

The heterogeneity in the immune response and efficiency of viral dissemination in brain infected with herpes simplex virus type 1 through peripheral or central route

Using immunohistochemistry on adjacent brain sections, we studied the correlation between the dissemination of the virus, the inflammatory responses and the expression of major histocompatibility complex (MHC) proteins in rat brain infected with herpes simplex virus (HSV-1) F strain by either corneal scarification or intracerebral injection. Our results showed that the mortality of the corneally infected rats was much higher than that of the intracerebrally infected rats, due to a more extensive dissemination of the virus in the brain, particularly in the brain stem. The inflammatory responses were similar in brains infected through either route, as demonstrated by the expression of MHC I/II antigens on infiltrating lymphocytes, leukocytes and macrophage/microglia cells. While there was strong immunoreactivity for HSV-1 antigens in the cerebral cortex, the infiltrates were only located in subcortical areas, especially the hippocampus. Therefore, the distribution of these immune cells did not always overlap with the regions of viral infection. These results suggest that HSV-1 disseminate more efficiently from the peripheral to the central nervous system (CNS) than from CNS to CNS, which is independent of the immune responses, and that the cerebral cortex may immunologically respond to HSV-1 infection differently from other brain regions. Received: 16 June 1998 / Revised: 22 October 1998 / Accepted: 11 November 1998     

Regulation of viral and cellular genes in a human neuroblastoma cell line latently infected with herpes simplex virus type 2

A latent state of the herpes simplex virus type 2 genome was established in a human neuroblastoma cell line (SMS-KCNR) to initiate studies on the mechanism by which host cells interact and regulate latent viral genes. To establish viral latency, it was necessary to prevent virus replication by briefly exposing the infected cells to antiherpetic acycloguanosine (20 microM) and human interferon (120 U/ml). Subsequently however, these cells could be propagated without any antiherpetic agents and almost 60% of the cell population contained viral genome. While these cells did not produce any infectious virus, immunoblot analysis revealed two intracellular polypeptides with molecular weights of 87.5 kDa and 67 kDa, respectively, that interacted with hyperimmune anti-HSV2 rabbit serum. Two cellular enzymes, acetylcholinesterase and choline acetyltransferase, involved in metabolism of neurotransmitters were expressed at a higher level in the latently infected cells than in the mock-infected control cells. Infectious HSV-2 could be reactivated from these cells only after the cells had undergone massive morphological differentiation and maturation to flat cell types by extensive treatment with 20 micron bromodeoxyuridine.     

Studies on the pathogenesis of and propagation of enterovirus 71 in poliomyelitis-like disease in monkeys

Summary Poliomyelitis-like disease in monkeys infected with enterovirus 71 (E71) were studied to determine whether nerve cell damage is due primarily to virus multiplication in the neurons or secondary to the effects of virus multiplication in the supporting tissue of the central nervous system (CNS). Monkeys infected with E71 develop a disease with neuromuscular or muscular dysfunction and lesions of the CNS. E71 was recovered from the lumbar and cervical cord and from the cerebrum. Specific immunofluorescence was detected in the degenerating or necrotic nerve cells in the anterior grey horns of the lumbar and cervical cord, the cerebellum and cerebrum, although virus antigen was not found in the white matter. No specific immunofluorescence was found in the glial cells, vascular endothelial or mononuclear inflammatory cells. From the present results, it is suggested that nerve cell damage is due principally to virus multiplication in the neurons of the CNS in monkeys infected with E71.