Slow Persistent Infection Caused by Visna Virus: Role of Host Restriction

Haase, Ashley T.; Stowring, Linda; Narayan, Opendra; Griffin, D. E.; Price, Donald L.

doi:10.1126/science.188133

Cited by 157 publications

(50 citation statements)

References 13 publications

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“…Virus gene expression in the brain of these sheep was detected by in situ hybridization and infectious virus was detected by coculture of brain homogenates with susceptible cells. The low level of detectable viral gene expression is consistent with the restricted viral replication that is the hallmark of lentivirus infection (Haase et al, 1976;Johnson et al, 1996). In vitro studies demonstrated that this brain-adapted virus replicated more ef®ciently in microglia and less ef®ciently in GSM than the parental virus.…”

Section: Discussionmentioning

confidence: 92%

Pathogenesis of ovine lentiviral encephalitis: Derivation of a neurovirulent strain by in vivo passage

Craig¹,

Sheffer²,

Meyer³

et al. 1997

J Neurovirol

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The lentiviruses of sheep replicate almost exclusively in macrophages and cause chronic interstitial pneumonia, arthritis, and mastitis, but only rarely encephalitis. This study was undertaken to determine whether a nonneurovirulent ®eld strain of ovine lentivirus isolated from joint¯uid that replicated productively in lung and joint macrophages could be adapted to enter and replicate in the brain and cause encephalitis. The ®eld isolate was passed seven times sequentially by intracerebral inoculation of sheep. The neuroadapted strain of virus caused severe encephalitis typical of visna in four of four sheep inoculated intracerebrally. The virus replicated to high titers in the brains of these animals and in cultured microglia. The in¯ammatory response in the brain was characterized by intense in®ltrates of macrophages and CD8 + and CD4 + T cells. Many of the perivascular macrophages demonstrated TNF-a expression and there was upregulation of MHC Class II antigen expression on both in¯ammatory cells and endothelium. Inoculation of this neuroadapted virus into the bone marrow of three animals resulted in persistent infection and cell-associated viremia, but not encephalitis. Virus was not detected in brains from these animals, indicating that the virus was not neuroinvasive. These data suggest that neuroinvasiveness and neurovirulence are separate pathogenic determinants, both of which are required for the development of encephalitis during natural infection.

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Section: Discussionmentioning

confidence: 92%

Pathogenesis of ovine lentiviral encephalitis: Derivation of a neurovirulent strain by in vivo passage

Craig¹,

Sheffer²,

Meyer³

et al. 1997

J Neurovirol

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“…However, the biologic relevance of these findings has been questioned by other workers who have discovered spread of virus in blood and CSF unabated by neutralizing antibodies (Petursson et al, 1976), long-term persistence of parental viral strains even after the appearance of variants (Lutley et al, 1983) and lack of antigenic variants in some animals even during advanced stages of disease (Thormar et al, 1983). Given the complexities of chronic retroviral-induced disease (Haase et al, 1977;Brahic et al, 1981;Stowring et al, 1985) it is likely that intrinsic viral characteristics as well as host-viral immune interactions play important roles in clinical outcome.…”

Section: Discussionmentioning

confidence: 97%

Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS

Starcich

Hahn

Shaw

et al. 1986

Cell

718

362

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SummaryTo determine the extent and nature of genetic variation present in independent isolates of HTLV-IIIILAV, the nucleotlde sequences of the entire envelope gene and parts of gag and pal were determined for two AIDS viruses. The results indicated that variation throughout the viral genome is extensive and that the envelope gene in particular is most highly variable. Within the envelope, changes were most prevalent within the extracellular region where clustered nucleotlde substitutions and deletlonslinsertlons were evident. Based on predicted secondary protein structure and hydrophillcity, these hypervariable reglons represent potential antigenic sites. In contrast to the hypervariable regions, other sequences in the extracellular envelope and the overall envelope structurrc (lncludlkg 18 of 18 cysteine residues), as well as most of the transmembrane region, were highly conserved.

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“…The lack of inflammation in the choroid plexus or any other part of the brain by routine histology, in conjunction with the morphological appearance of the labelled cells makes it very unlikely that these cells are other than choroid plexus epithelial cells. The presence of SRV-1 in such cells was not entirely unexpected since retroviral infection of the choroid plexus has been demonstrated in visna of sheep (Haase et al, 1977) and because it is a pathway into the brain (Levine, 1987). In addition, SRV-1 has a broad cellular tropism in vivo (Maul et al, 1988) and an affinity for secretory epithelium such as salivary gland acinar cells (Lackner et al, 1988;Lerche et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…As shown by immunohistochemistry, the apparent source of the virus is relatively rare infected choroid plexus epithelial cells. Whether or not there is restriction of viral replication in other choroid plexus cells as there is for visna virus (Haase et al, 1977) awaits future studies involving combined in situ hybridization and immunohistochemistry. The lack of inflammation in the choroid plexus or any other part of the brain by routine histology, in conjunction with the morphological appearance of the labelled cells makes it very unlikely that these cells are other than choroid plexus epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Choroid plexus was chosen because it has been shown to be a target for systemic disease and a pathway to the brain (Levine, 1987). In addition, the choroid plexus has been shown to be a key site for replication of visna virus (Haase et al, 1977). Eight of the viraemic animals were from group 1 and one was from group 2, All of the viraemic animals had SRV-1 cultured from their CSF except 8016, Examination of axillary lymph node and spleen tissue provided internal positive controls.…”

Section: Immunohistochemistry For Sr V-1mentioning

confidence: 99%

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Asymptomatic Infection of the Central Nervous System by the Macaque Immunosuppressive Type D Retrovirus, SRV-1

Lackner¹,

Marx

Lerche

et al. 1989

Journal of General Virology

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SUMMARYThe aetiological agent of spontaneously occurring simian acquired immune deficiency syndrome (SAIDS) in rhesus monkeys (Macaca mulatta) at the California Primate Research Center is a type D retrovirus designated SAIDS retrovirus serotype 1 (SRV-1). SRV-1 DNA and RNA have previously been detected in the brains of rhesus monkeys with SAIDS in the absence of viral antigen or neuropathological lesions. In this study we further define the relationship between SRV-1 and the central nervous system (CNS) in rhesus monkeys by examining the CNS for infectious SRV-1, viral antigen and anti-SRV-1 antibodies. In addition, cerebrospinal fluid (CSF) was assayed for alterations in IgG and albumin levels, IgG/albumin ratios and cell count in comparison to uninfected control animals. No differences in CSF parameters were detected between infected and uninfected animals except for the presence of infectious SRV-1 which was isolated from the CSF from 13 out of 19 (68%) viraemic rhesus monkeys. The probable source of this virus was the choroid plexus, where approximately 1 in 1000 surface epithelial cells were found to contain viral antigen by immunohistochemistry. Antibodies against SRV-1 were not detected in the CSF even when present in the serum. Neither infectious virus nor viral antigen were found in the brain parenchyma of any animal examined. Thus infection of the CNS by SRV-1 appears to be subclinical without an intrathecal immune response. This may be related to the apparent restriction of productive infection in the CNS to cells of the choroid plexus.

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Slow Persistent Infection Caused by Visna Virus: Role of Host Restriction

Cited by 157 publications

References 13 publications

Pathogenesis of ovine lentiviral encephalitis: Derivation of a neurovirulent strain by in vivo passage

Pathogenesis of ovine lentiviral encephalitis: Derivation of a neurovirulent strain by in vivo passage

Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS

Asymptomatic Infection of the Central Nervous System by the Macaque Immunosuppressive Type D Retrovirus, SRV-1

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