Herpes simplex virus induces neural oxidative damage via microglial cell Toll-like receptor-2

Schachtele, Scott J.; Hu, Shuxian; Little, Morgan R.; Lokensgard, James R.

doi:10.1186/1742-2094-7-35

Cited by 88 publications

(76 citation statements)

References 31 publications

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“…Axonal swellings with 4-HNE-labelled puncta were also associated with aggregations of actively respiring mitochondria, and there is recent evidence that 4-HNE directly impairs mitochondrial function in cultured dorsal root ganglion neurons. 52 In addition to our findings in rabies virus infection, oxidative stress has been recognized to be an important component of experimental acute encephalitis caused by herpes simplex virus type 1 in mice [53][54][55] and also plays a role in neurodegeneration in a variety of diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and diabetic neuropathy.…”

Section: New Insights Concerning Neuronal Processessupporting

confidence: 56%

Update on rabies

Jackson¹

2011

RRTM

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Human rabies is almost invariably fatal, and globally it remains an important public health problem. Our knowledge of rabies pathogenesis has been learned mainly from studies performed in experimental animal models, and a number of unresolved issues remain. In contrast with the neural pathway of spread, there is still no credible evidence that hematogenous spread of rabies virus to the central nervous system plays a significant role in rabies pathogenesis. Although neuronal dysfunction has been thought to explain the neurological disease in rabies, recent evidence indicates that structural changes involving neuronal processes may explain the severe clinical disease and fatal outcome. Endemic dog rabies results in an ongoing risk to humans in many resource-limited and resource-poor countries, whereas rabies in wildlife is important in North America and Europe. In human cases in North America, transmission from bats is most common, but there is usually no history of a bat bite and there may be no history of contact with bats. Physicians may not recognize typical features of rabies in North America and Europe. Laboratory diagnostic evaluation for rabies includes rabies serology plus skin biopsy, cerebrospinal fluid, and saliva specimens for rabies virus antigen and/or RNA detection. Methods of postexposure rabies prophylaxis, including wound cleansing and administration of rabies vaccine and human rabies immune globulin, are highly effective after recognized exposure. Although there have been rare survivors of human rabies, no effective therapy is presently available. Therapeutic coma (midazolam and phenobarbital), ketamine, and antiviral therapies (known as the "Milwaukee protocol") were given to a rabies survivor, but this therapy was likely not directly responsible for the favorable outcome. New therapeutic approaches for human rabies need to be developed. A better understanding of basic mechanisms involved in rabies pathogenesis may be helpful in the development of potential new therapies for the future.

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Section: New Insights Concerning Neuronal Processessupporting

confidence: 56%

Update on rabies

Jackson¹

2011

RRTM

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“…(60), and glycoprotein gJ has been shown to induce ROS production (61). HSV-1 infection of microglia induced a rapid 1.5-fold in- crease in ROS production as early as 3 h p.i., and ROS production was more robust at 24 h p.i., with a 2-fold increase (62,63). ROS production after HSV-1 infection was dependent on NADPH oxidase activity.…”

Section: Discussionmentioning

confidence: 91%

Reactive Oxygen Species Are Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during Primary Infection of Endothelial Cells To Promote Virus Entry

Bottero

Chakraborty

Chandran

2013

J Virol

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“…The zinc finger motif of Hsp33 is not found in eukaryotic proteins (70) but is similar to a cysteine motif in the regulatory domain of UL16 (6). Moreover, it is known that HSV infections induce and require oxidative stress for the production of infectious virions (71)(72)(73)(74)(75)(76)(77)(78). But unlike those of Hsp33, the binding activities of the N-terminal portion of UL16 seem to be specific for particular viral proteins: UL11 (6), gE (9), and VP22 (this study).…”

Section: Discussionmentioning

confidence: 99%

Elucidation of the Block to Herpes Simplex Virus Egress in the Absence of Tegument Protein UL16 Reveals a Novel Interaction with VP22

Starkey

Han

Chadha

et al. 2014

J Virol

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UL16 is a tegument protein of herpes simplex virus (HSV) that is conserved among all members of the Herpesviridae, but its function is poorly understood. Previous studies revealed that UL16 is associated with capsids in the cytoplasm and interacts with the membrane protein UL11, which suggested a "bridging" function during cytoplasmic envelopment, but this conjecture has not been tested. To gain further insight, cells infected with UL16-null mutants were examined by electron microscopy. No defects in the transport of capsids to cytoplasmic membranes were observed, but the wrapping of capsids with membranes was delayed. Moreover, clusters of cytoplasmic capsids were often observed, but only near membranes, where they were wrapped to produce multiple capsids within a single envelope. Normal virion production was restored when UL16 was expressed either by complementing cells or from a novel position in the HSV genome. When the composition of the UL16-null viruses was analyzed, a reduction in the packaging of glycoprotein E (gE) was observed, which was not surprising, since it has been reported that UL16 interacts with this glycoprotein. However, levels of the tegument protein VP22 were also dramatically reduced in virions, even though this gE-binding protein has been shown not to depend on its membrane partner for packaging. Cotransfection experiments revealed that UL16 and VP22 can interact in the absence of other viral proteins. These results extend the UL16 interaction network beyond its previously identified binding partners to include VP22 and provide evidence that UL16 plays an important function at the membrane during virion production. Infectious herpesviruses contain approximately 40 viral proteins and are produced when their DNA-containing capsids are wrapped with a cell-derived membrane in the cytoplasm (1). This envelopment process is driven by complex interactions that are still poorly understood but is known to involve bridging interactions provided by a growing list of tegument proteins, which provide linkages between the capsid and viral membrane proteins (1-3). The UL16 tegument protein of herpes simplex virus (HSV) is remarkable for its numerous interactions with several other viral proteins, namely, tegument protein UL21 (4, 5), membrane protein UL11 (4, 6-8), membrane glycoprotein E (gE) (4, 9), and an unidentified protein(s) that is associated with the capsid (10-12). UL16 is conserved among all the alpha-, beta-, and gammaherpesvirinae (2, 13, 14), but its actual function remains unknown.There are several reasons for suggesting a role for UL16 in HSV envelopment. The earliest study showed that a U L 16-null mutant (here named the ⌬U L 16B mutant) produces infectious virions at a level only one-tenth that of the wild-type virus (15). Also, UL16 has been shown to be bound in some manner to cytoplasmic capsids (10, 16, 17), and thus, its direct interactions with membrane proteins UL11 (8) and gE (9) suggest that UL16 might provide bridging functions that help drive virion production, as first pro...

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Herpes simplex virus induces neural oxidative damage via microglial cell Toll-like receptor-2

Cited by 88 publications

References 31 publications

Update on rabies

Update on rabies

Reactive Oxygen Species Are Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during Primary Infection of Endothelial Cells To Promote Virus Entry

Elucidation of the Block to Herpes Simplex Virus Egress in the Absence of Tegument Protein UL16 Reveals a Novel Interaction with VP22

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