Immunohistochemical approach to the pathogenesis of clinical cases of Bovine Herpesvirus type 5 infections

Cardoso, Tereza Cristina; Ferrari, Heitor F.; Garcia, Andrea F.; Bregano, Lívia C.; Andrade, Alexandre Lima de; Nogueira, Adriana Hc

doi:10.1186/1746-1596-5-57

Cited by 13 publications

(9 citation statements)

References 20 publications

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“…Previous studies revealed that mitochondrial membrane potential can be altered without affecting non-transformed cellular cycle after infected by BHV5 (Brenner et al 2012;Garcia et al 2013). The expression of anti-oxidant protein-like 1 (AOP-1), a protective pathway, has been detected in bovine embryos and brain histological sections, both infected by BHV5 (Brenner et al 2012;Cardoso et al 2010). Furthermore, increase of mitochondrial membrane potential could be associated to virus replication and not always associated to cell death (Hay and Kannourakis 2002).…”

Section: Discussionmentioning

confidence: 96%

Bovine herpesviruses induce different cell death forms in neuronal and glial-derived tumor cell cultures

et al. 2016

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Oncolytic viruses have the ability to infect tumor cells and leave healthy cells intact. In this study, bovine herpesvirus 1 (BHV1; Los Angeles, Cooper, and SV56/90 strains) and bovine herpesvirus 5 (BHV5; SV507/99 and GU9457818 strains) were used to infect two neuronal tumor cell lineages: neuro2a (mouse neuroblastoma cells) and C6 (rat glial cells). BHV1 and BHV5 strains infected both cell lines and positively correlated with viral antigen detection (p < 0.005). When neuro2a cells were infected by Los Angeles, SV507/99, and GU9457818 strains, 40 % of infected cells were under early apoptosis and necroptosis pathways. Infected C6 cells were >40 % in necroptosis phase when infected by BHV5 (GU9457818 strain). Blocking caspase activation did not interfere with cell death. However, when necroptosis was blocked, 60-80 % of both infected cells with either virus switched to early apoptosis pathway with no interference with virus replication. Moreover, reactive oxygen species production and mitochondrial membrane dysfunction were detected at high levels in both infected cell lines. In spite of apoptosis and necroptosis blockage, tumor necrosis factor alpha (TNFA) and virus transcription were positively correlated for all viral strains studied. Thus, these results contribute to the characterization of BHV1 and BHV5 as potential oncolytic viruses for non-human cells. Nonetheless, the mechanisms underlying their oncolytic activity in human cells are still to be determined.

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Section: Discussionmentioning

confidence: 96%

Bovine herpesviruses induce different cell death forms in neuronal and glial-derived tumor cell cultures

et al. 2016

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“…Indeed, rabbits have been used as an animal model to study selected aspects of acute and latent infections caused by BoHV-5 [19]. Unlike BoHV-1, BoHV-5 can be difficult to isolate from cell culture and animals presenting neurological symptoms after experimental inoculation [20-23]. These difficulties in viral isolation might be related to low virus titres present in tissue sections [18].…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of neuron-like cells derived from bovine Wharton’s jelly to bovine herpesvirus type 5 infections

et al. 2012

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BackgroundBovine herpesvirus type 5 (BoHV-5), frequently lethal in cattle, is associated with significant agricultural economic losses due to neurological disease. Cattle and rabbits are frequently used as models to study the biology and pathogenesis of BoHV-5 infection. In particular, neural invasion and proliferation are two of the factors important in BoHV-5 infection. The present study investigated the potential of bovine Wharton’s jelly mesenchymal stromal cells (bWJ-MSCs) to differentiate into a neuronal phenotype and support robust BoHV-5 replication.ResultsUpon inducing differentiation within a defined neuronal specific medium, most bWJ-MSCs acquired the distinctive neuronal morphological features and stained positively for the neuronal/glial markers MAP2 (neuronal microtubule associated protein 2), N200 (neurofilament 200), NT3 (neutrophin 3), tau and GFAP (glial fibrillary acidic protein). Expression of nestin, N200, β-tubulin III (TuJI) and GFAP was further demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR). Following BoHV-5 inoculation, there were low rates of cell detachment, good cell viability at 96 h post-infection (p.i.), and small vesicles developed along neuronal branches. Levels of BoHV-5 antigens and DNA were associated with the peak in viral titres at 72 h p.i. BoHV-5 glycoprotein C mRNA expression was significantly correlated with production of progeny virus at 72 h p.i. (p < 0.05).ConclusionThe results demonstrated the ability of bWJ-MSCs to differentiate into a neuronal phenotype in vitro and support productive BoHV-5 replication. These findings constitute a remarkable contribution to the in vitro study of neurotropic viruses. This work may pave the way for bWJ-MSCs to be used as an alternative to animal models in the study of BoHV-5 biology.

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“…Finally, it has been postulated that bovine herpesvirus 5 (BHV-5) entry the CNS is facilitated by leukocytes and MMP9. However, induction of MMP9 expression by BHV-5 has not been directly demonstrated so far [75].…”

Section: The Heterogeneous Molecule: Proteoglycanmentioning

confidence: 99%

“…The closely related EHV-4 did not efficiently infect these local immune cells, which might be the reason why EHV-4-induced viremia is rare [98]. It has been postulated that BHV-5 might use a similar invasive mechanism as EHV-1 and that BHV-5 entry into the CNS is facilitated by leukocytes and MMP9 [75]. Lymphocytemediated viral entry into the brain has also been demonstrated for HTLV-1 [70].…”

Section: The Heterogeneous Molecule: Proteoglycanmentioning

confidence: 99%

Diverse microbial interactions with the basement membrane barrier

Steukers¹,

Glorieux²,

Vandekerckhove

et al. 2012

Trends in Microbiology

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During primary contact with susceptible hosts, microorganisms face an array of barriers that thwart their invasion process. Passage through the basement membrane (BM), a 50-100-nm-thick crucial barrier underlying epithelia and endothelia, is a prerequisite for successful host invasion. Such passage allows pathogens to reach nerve endings or blood vessels in the stroma and to facilitate spread to internal organs. During evolution, several pathogens have developed different mechanisms to cross this dense matrix of sheet-like proteins. To breach the BM, some microorganisms have developed independent mechanisms, others hijack host cells that are able to transverse the BM (e.g. leukocytes and dendritic cells) and oncogenic microorganisms might even trigger metastatic processes in epithelial cells to penetrate the underlying BM.

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Immunohistochemical approach to the pathogenesis of clinical cases of Bovine Herpesvirus type 5 infections

Cited by 13 publications

References 20 publications

Bovine herpesviruses induce different cell death forms in neuronal and glial-derived tumor cell cultures

Bovine herpesviruses induce different cell death forms in neuronal and glial-derived tumor cell cultures

Susceptibility of neuron-like cells derived from bovine Wharton’s jelly to bovine herpesvirus type 5 infections

Diverse microbial interactions with the basement membrane barrier

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