Bovine herpesviruses induce different cell death forms in neuronal and glial-derived tumor cell cultures.
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.
DAPSA Department, Laboratory of Animal Virology and Cell Culture, College of Veterinary Medicine, Universidade Estadual Paulista, Araçatuba, São Paulo, 16050-680, Brazil. tcardoso@fmva.unesp.br.
Tereza C
TC
Cardoso
DAPSA Department, Laboratory of Animal Virology and Cell Culture, College of Veterinary Medicine, Universidade Estadual Paulista, Araçatuba, São Paulo, 16050-680, Brazil.
Ana Carolina G
AC
Rosa
DAPSA Department, Laboratory of Animal Virology and Cell Culture, College of Veterinary Medicine, Universidade Estadual Paulista, Araçatuba, São Paulo, 16050-680, Brazil.|FZEA-USP, Departamento de Medicina Veterinária, Av. Duque de Caxias Norte, 225, Pirassununga, SP, CEP 13635-900, Brazil.
Helena L
HL
Ferreira
DAPSA Department, Laboratory of Animal Virology and Cell Culture, College of Veterinary Medicine, Universidade Estadual Paulista, Araçatuba, São Paulo, 16050-680, Brazil.
Lucas H
LH
Okamura
DAPSA Department, Laboratory of Animal Virology and Cell Culture, College of Veterinary Medicine, Universidade Estadual Paulista, Araçatuba, São Paulo, 16050-680, Brazil.
Bruna R S M
BR
Oliveira
DAPSA Department, Laboratory of Animal Virology and Cell Culture, College of Veterinary Medicine, Universidade Estadual Paulista, Araçatuba, São Paulo, 16050-680, Brazil.
Flavia V
FV
Vieira
DAPSA Department, Laboratory of Animal Virology and Cell Culture, College of Veterinary Medicine, Universidade Estadual Paulista, Araçatuba, São Paulo, 16050-680, Brazil.
Camila
C
Silva-Frade
DAPSA Department, Laboratory of Animal Virology and Cell Culture, College of Veterinary Medicine, Universidade Estadual Paulista, Araçatuba, São Paulo, 16050-680, Brazil.
Roberto
R
Gameiro
Virology Section, Federal University of Santa Maria, Santa Maria, 97115-900, RS, Brazil.
Eduardo F
EF
Flores
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D002417:Cattle; D045744:Cell Line, Tumor; D015870:Gene Expression; D007242:Herpesvirus 1, Bovine / Q000235:genetics / Q000254:growth & development*; D025881:Herpesvirus 5, Bovine / Q000235:genetics / Q000254:growth & development*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000821:virology; D009336:Necrosis / Q000235:genetics / Q000473:pathology / Q000821:virology*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D050504:Oncolytic Viruses / Q000235:genetics / Q000254:growth & development; D009928:Organ Specificity; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D000956:Antigens, Viral; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha
Animal herpesvirus; Apoptosis; Necroptosis; Oncolytic viruses; Oxidative stress; Pathogenesis