A bovine herpesvirus 5 recombinant defective in the thymidine kinase (TK) gene and a double mutant lacking TK and the glycoprotein E gene are fully attenuated for rabbits

Silva, S.C.; Brum, Mário Celso Sperotto; Weiblen, Rudi; Flores, Eduardo Furtado; Chowdhury, Shafiqul I.

doi:10.1590/s0100-879x2009007500030

Cited by 10 publications

(30 citation statements)

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“…The results presented herein confirm and extend previous observations (Silva et al 2010) which indicate that the recombinant is fully attenuated for rabbits after IN inoculation. Interestingly, the recombinant retains the ability to invade and to replicate to a certain extent in the CNS during acute infection, albeit without producing neurological disease.…”

Section: Introductionsupporting

confidence: 91%

“…Similarly, an HSV-1 TK negative strain was able to replicate in the cornea of rats in lower levels than the wild type virus (Chen et al 2004). In recent experiment the recombinant BoHV-5TKΔ was shown to replicate less efficiently (both in titer and duration) than the parental virus in the nasal mucosa of experimentally infected calves (Santos et al 2010) and rabbits (Silva et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…This recombinant was constructed out of a neurovirulent Brazilian BoHV-5 strain and was previously shown to be attenuated for rabbits (Silva et al 2010) and calves (Santos et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…In a previous studies, a Brazilian BoHV-5 TK negative strain (BoHV-5TKΔ) was shown to be attenuated in a rabbit model (Silva et al 2010) and a BoHV-5 brivudin-resistant strainprobably defective in TK activity-was also attenuated in rabbits (Brum et al 2009). However, in none of these studies the ability of the virus to spread into the CNS following IN inoculation was addressed.…”

Section: Introductionmentioning

confidence: 95%

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A thymidine kinase-negative bovine herpesvirus 5 is highly attenuated for rabbits, but is neuroinvasive and establishes latent infection

et al. 2011

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ABSTRACT.-Silva S.C., Brum M.C.S., Oliveira S.A.M., Weiblen R. & Flores E.F. 2011. A thymidine kinase-negative bovine herpesvirus 5 is highly attenuated for rabbits, but is neuroinvasive and establishes latent infection. Pesquisa Veterinária Brasileira 31(5):389-397. Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Camobi, Santa Maria, Mutant viral strains deleted in non-essential genes represent useful tools to study the function of specific gene products in the biology of the virus. We herein describe an investigation on the phenotype of a bovine herpesvirus 5 (BoHV-5) recombinant deleted in the gene encoding the enzyme thymidine kinase (TK) in rabbits, with special emphasis to neuroinvasiveness and the ability to establish and reactivate latent infection. Rabbits inoculated with the parental virus (SV-507/99) (n=18) at a low titer (10 TCID 50 ) and for a shorter period (average: 6.6 days [2-11]) and remained healthy. PCR examination of brain sections of inoculated rabbits at day 6 post-infection (pi) revealed a widespread distribution of the parental virus, whereas DNA of the recombinant BoHV-5TKΔ-was detected only in the trigeminal ganglia [TG] and olfactory bulbs [OB]. Nevertheless, during latent infection (52pi), DNA of the recombinant virus was detected in the TGs, OBs and also in other areas of the brain, demonstrating the ability of the virus to invade the brain. Dexamethasone (Dx) administration at day 65 pi was followed by virus reactivation and shedding by 5/8 rabbits inoculated with the parental strain (mean duration of 4.2 days [1 -9]) and by none of seven rabbits inoculated with the recombinant virus. Again, PCR examination at day 30 post-Dx treatment revealed the presence of latent DNA in the TGs, OBs and in other areas of the brain of both groups. Taken together, these results confirm that the recombinant BoHV-5TKΔ is highly attenuated for rabbits. It shows a reduced ability to replicate in the nose but retains the ability to invade the brain and to establish latent infection. Additional studies are underway to determine the biological and molecular mechanisms underlying the inability of BoHV-5TKΔ to reactivate from latency.

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Section: Introductionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

“…This recombinant was constructed out of a neurovirulent Brazilian BoHV-5 strain and was previously shown to be attenuated for rabbits (Silva et al 2010) and calves (Santos et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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A thymidine kinase-negative bovine herpesvirus 5 is highly attenuated for rabbits, but is neuroinvasive and establishes latent infection

et al. 2011

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“…Apesar de sua extensiva caracterização, a cepa SV-507/99 ainda não havia sido inoculada em ovinos, desconhecendo-se a sua biologia e o seu potencial neurovirulento nessa espécie; (ii) a cepa SV-507/99 tem sido alvo de manipulação genética para a produção de mutantes defectivos em genes especíϐicos, como a glicoproteína E (gE) e enzima timidina quinase (TK), e ambos gE/TK . O fenótipo desses recombinantes tem sido estudado em coelhos (Silva et al 2010) e em bezerros (Santos et al 2010). Os recombinantes defectivos na gE, TK e ambos gE/TK também tem sido avaliados como candidatos a cepas vacinais (Anziliero et al 2011).…”

Section: Discussionunclassified

Reativação e distribuição do DNA latente do herpesvírus bovino tipo 5 no encéfalo de ovinos infectados experimentalmente

et al. 2011

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Pesq. Vet. Bras. 31(12):1090-1096, dezembro 2011 1090 RESUMO.-A biologia da infecção latente pelo herpesvírus bovino tipo 5 (BoHV-5) tem sido estudada em bovinos e coelhos, mas vários aspectos permanecem desconhecidos. Este artigo relata uma avaliação de ovinos jovens como modelo para o estudo da infecção latente pelo The biology of latent infection by bovine herpesvirus type 5 (BoHV-5) has been studied in cattle and rabbits, yet many aspects remain poorly understood. We herein investigated the suitability of lambs to investigate aspects of BoHV-5 latency. Thirteen six-month-old lambs inoculated intranasally (IN) with BoHV-5 strain SV-507/99 (titer of 10 6.8 TCID 50 / mL) shed the virus in nasal secretions in titers up 10 5.5 TCID 50 /mL, during up to 11 days, developing virus neutralizing (VN) titers of 16 to 128 at day 30 post-inoculation (pi). The inoculated animals developed only a mild serous nasal secretion and transient hyperthermia. Examination of brain sections of ϐive lambs euthanized at day 30 pi by PCR revealed the presence of latent DNA in the trigeminal ganglia (TG, 5 out of ϐive), olfactory bulbs (OB, 5/5), pons (2/5), cerebellum (2/5) and cerebral cortex (1/5). Administration of dexamethasone (Dx, n=4) or ϐlumethasone (FluM, n=4) to eight latently infected lambs at day 65 pi resulted in virus reactivation and shedding by 3 out of 4 individuals in each group. Virus shedding in nasal secretions started at day 3 post-treatment and lasted up to ϐive days (1-5) in Dx treated lambs (titers up to 10 2.8 TCID 50 /mL), was delayed and lasted up to three days (1-3) in FluM-treated lambs (titers up to 10 2.1 TCID 50 /mL). PCR examination of the brains of animals submitted to reactivation, at day 30 post-treatment, showed a pattern of distribution of latent viral DNA fairly similar to that found in those not submitted to reactivation. In summary, the ability of BoHV-5 to establish latent infection, the consistent colonization of TGs and OBs by latent viral DNA and virus reactivation induced by corticosteroid treatment are promising ϐindings towards the use of lambs to study selected aspects of BoHV-5 latency.

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Protective immunity following vaccination with a recombinant multiple-epitope protein of bovine herpesvirus type I in a rabbit model

Wen

Tong

Wang

et al. 2020

Appl Microbiol Biotechnol

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Bovine herpesvirus type 1 (BoHV-1) causes considerable economic losses to the cow industry. Vaccination remains an effective strategy to control the diseases associated with BoHV-1. However, live vaccines present safety concerns, especially in pregnant cows; thus, nonreplicating vaccines have been developed to control the disease. The envelope glycoproteins of BoHV-1 induce a protective immune response. In this work, selected epitopes on glycoproteins gD, gC, and gB were constructed in triplicate with linker peptides. Vaccination of rabbits demonstrated that P2-gD/gC/gB with AAYAAY induced higher specific antibodies than that with GGGGS linker. P2-gD/gC/gB with AAYAAY linker was fused with bovine interleukin-6 (BoIL-6) or rabbit IL-6 (RaIL-6) and bacterially expressed. Rabbits were intramuscularly immunized with 100 μg of P2-gD/gC/gB-BoIL-6, P2-gD/gC/gB-RaIL-6, P2-gD/gC/gB, P2-gD/gC/gB plus BoIL-6, P2-(gD-a)3-BoIL-6, or P2-(gD-a)3 emulsified with ISA 206 adjuvant thrice at 3-week intervals. P2-gD/gC/gB-BoIL-6 generated a higher titer of BoHV-1-specific antibodies, neutralizing antibodies, interferon (IFN)-γ, and IL-4 compared with P2-gD/gC/gB plus BoIL-6, P2-gD/gC/gB-RaIL-6, or other formulation. P2-gD/gC/gB-BoIL-6 triggered similar levels of antibodies and significantly higher titer of IFN-γ and IL-4 compared with inactivated bovine viral diarrhea (BVD)-infectious bovine rhinotracheitis (IBR) vaccine. Rabbits vaccinated with P2-gD/gC/gB-BoIL-6 dramatically reduced viral shedding and tissue lesions in lungs and trachea after viral challenge and reactivation compared with those with P2-gD/gC/gB plus BoIL-6 or P2-gD/gC/gB-RaIL-6. P2-gD/gC/gB-BoIL-6 provided protective effects against viral shedding and tissue pathogenesis similar to those of the inactivated vaccine. The data confirmed the safety and immunogenicity of multiple-epitope recombinant protein and a potential vaccine candidate to control the disease, especially for pregnant cattle.

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A bovine herpesvirus 5 recombinant defective in the thymidine kinase (TK) gene and a double mutant lacking TK and the glycoprotein E gene are fully attenuated for rabbits

Cited by 10 publications

References 38 publications

A thymidine kinase-negative bovine herpesvirus 5 is highly attenuated for rabbits, but is neuroinvasive and establishes latent infection

A thymidine kinase-negative bovine herpesvirus 5 is highly attenuated for rabbits, but is neuroinvasive and establishes latent infection

Reativação e distribuição do DNA latente do herpesvírus bovino tipo 5 no encéfalo de ovinos infectados experimentalmente

Protective immunity following vaccination with a recombinant multiple-epitope protein of bovine herpesvirus type I in a rabbit model

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