scholarly journals Bovine Herpesvirus 1 Can Infect CD4+ T Lymphocytes and Induce Programmed Cell Death during Acute Infection of Cattle

1999 ◽  
Vol 73 (10) ◽  
pp. 8657-8668 ◽  
Author(s):  
M. T. C. Winkler ◽  
A. Doster ◽  
C. Jones
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Acute Infection ◽  
Bovine Herpesvirus ◽  
Cell Mediated Immunity ◽  
Apoptotic Cells ◽  
Bovine Herpesvirus 1 ◽  
Herpesvirus 1 ◽  
Pharyngeal Tonsil

ABSTRACT Acute infection of cattle with bovine herpesvirus 1 (BHV-1) represses cell-mediated immunity, which can lead to secondary bacterial infections. Since BHV-1 can induce apoptosis of cultured lymphocytes, we hypothesized that these virus-host interactions occur in cattle. To test this hypothesis, we analyzed lymph nodes and peripheral blood mononuclear cells (PBMC) after calves were infected with BHV-1. In situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) staining of lymphoid tissues (pharyngeal tonsil, cervical, retropharyngeal, and inguinal) was used to detect apoptotic cells. Calves infected with BHV-1 for 7 days revealed increased apoptotic cells near the corticomedullary junction in lymphoid follicles and in the subcapsular region. Increased frequency of apoptotic cells was also observed in the mucosa-associated lymphoid tissue lining the trachea and turbinate. Immunohistochemistry of consecutive sections from pharyngeal tonsil revealed that CD2+ T lymphocytes were positive for the BHV-1 envelope glycoprotein gD. The location of these CD2+ T lymphocytes in the germinal center suggested that they were CD4+ T cells. Electron microscopy and TUNEL also revealed apoptotic and herpesvirus-infected lymphocytes from this area. Fluorescence-activated cell sorting analyses demonstrated that CD4+ and CD8+ T cells decreased in lymph nodes and PBMC after infection. The decrease in CD4+ T cells correlated with an increase in apoptosis. CD4+ but not CD8+ lymphocytes were infected by BHV-1 as judged by in situ hybridization and PCR, respectively. Immediate-early (bovine ICP0) and early (ribonucleotide reductase) transcripts were detected in PBMC and CD4+ lymphocytes prepared from infected calves. In contrast, a late transcript (glycoprotein C) was not consistently detected suggesting productive infection was not efficient. Taken together, these results indicate that BHV-1 can infect CD4+T cells in cattle, leading to apoptosis and suppression of cell-mediated immunity.

scholarly journals Susceptibility of Bovine Antigen-Presenting Cells to Infection by Bovine Herpesvirus 1 and In Vitro Presentation to T Cells: Two Independent Events

1999 ◽  
Vol 73 (6) ◽  
pp. 4840-4846 ◽  
Author(s):  
Ximena Renjifo ◽  
Carine Letellier ◽  
Günther M. Keil ◽  
Jamila Ismaili ◽  
Alain Vanderplasschen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Bovine Herpesvirus ◽  
T Cell Proliferation ◽  
Bovine Herpesvirus 1 ◽  
Herpesvirus 1 ◽  
Antigen Presenting

ABSTRACT The aim of the present study was to develop an in vitro system for presentation of bovine herpesvirus 1 (BHV-1) antigens to bovine T lymphocytes and to characterize the antigen-presenting cells (APC) which efficiently activate CD4+ T cells. Two approaches were used to monitor the infection of APC by BHV-1 as follows: (i) detection of viral glycoproteins at the cell surface by immunofluorescence staining and (ii) detection of UL26 transcripts by reverse transcription-PCR. The monocytes were infected, while dendritic cells (DC) did not demonstrate any detectable viral expression. These data suggest that monocytes are one site of replication, while DC are not. The capacities of monocytes and DC to present BHV-1 viral antigens in vitro were compared. T lymphocytes (CD2+ or CD4+) from BHV-1 immune cattle were stimulated in the presence of APC previously incubated with live or inactivated wild-type BHV-1. DC stimulated strong proliferation of Ag-specific T cells, while monocytes were poor stimulators of T-cell proliferation. When viral attachment to the surface of the APC was inhibited by virus pretreatment with soluble heparin, T-cell proliferation was dramatically decreased. Unexpectedly, incubation of DC and monocytes with the deletion mutant BHV-1 gD−/−, which displays impaired fusion capacity, resulted in strong activation of T lymphocytes by both APC types. Collectively, these results indicate that presentation of BHV-1 antigens to immune T cells is effective in the absence of productive infection and suggest that BHV-1 gD−/− mutant virus could be used to induce virus-specific immune responses in cattle.

scholarly journals Safety and immunogenicity of a glycoprotein E gene-deleted bovine herpesvirus 1 strain as a candidate vaccine strain

2016 ◽  
Vol 36 (11) ◽  
pp. 1067-1074
Author(s):  
Marcelo Weiss ◽  
◽  
Deniz Anziliero ◽  
Mathias Martins ◽  
Rudi Weiblen ◽  
...  
Keyword(s):  
Acute Infection ◽  
Clinical Signs ◽  
Bovine Herpesvirus ◽  
Elisa Test ◽  
Bovine Herpesvirus 1 ◽  
Glycoprotein E ◽  
Virus Shedding ◽  
Group I ◽  
Virus Dose ◽  
Herpesvirus 1

ABSTRACT: A glycoprotein E-deleted Brazilian bovine herpesvirus 1 (BoHV-1gEΔ) was tested regarding to safety and immunogenicity. Intramuscular inoculation of young calves with a high virus dose did not result in clinical signs or virus shedding during acute infection or after dexamethasone administration. Calves vaccinated once IM (group I) or subcutaneously (group II) with live BoHV-1gEΔ or twice with inactivated virus plus aluminum hydroxide (group IV) or Montanide™ (group V) developed VN titers of 2 to 8 (GMT:2); 2 to 4 (GMT:1.65); 2 to 16 (GMT:2.45) and 2 to 128 (GMT:3.9), respectively. All BoHV-1gEΔ vaccinated calves remained negative in an anti-gE ELISA. Lastly, six young calves vaccinated with live BoHV-1gEΔ and subsequently challenged with a virulent BoHV-1 strain shed less virus and developed only mild and transient nasal signs comparing to unvaccinated calves. Thus, the recombinant BoHV-1gEΔ is safe and immunogenic for calves and allows for serological differentiation by a gE-ELISA test.

scholarly journals Bovine herpesvirus-1-induced pharyngeal tonsil lesions in neonatal and weanling calves

1992 ◽  
Vol 106 (3) ◽  
pp. 243-253 ◽  
Author(s):  
J.C.L. Schuh ◽  
H. Bielefeldt Ohmann ◽  
L.A. Babiuk ◽  
C.E. Doige
Keyword(s):  
Bovine Herpesvirus ◽  
Bovine Herpesvirus 1 ◽  
Herpesvirus 1 ◽  
Pharyngeal Tonsil

Immunity to bovine herpesvirus 1: II. Adaptive immunity and vaccinology

2013 ◽  
Vol 14 (1) ◽  
pp. 103-123 ◽  
Author(s):  
Randall L. Levings ◽  
James A. Roth
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Cytotoxic T Lymphocyte ◽  
Clinical Signs ◽  
Human Herpesvirus ◽  
Bovine Herpesvirus ◽  
Genetically Engineered ◽  
Cell Mediated Immunity ◽  
Bovine Herpesvirus 1 ◽  
Herpesvirus 1

AbstractBovine herpesvirus 1 (BHV-1) infection is widespread and causes a variety of diseases. Although similar in many respects to the human immune response to human herpesvirus 1, the differences in the bovine virus proteins, immune system components and strategies, physiology, and lifestyle mean the bovine immune response to BHV-1 is unique. The innate immune system initially responds to infection, and primes a balanced adaptive immune response. Cell-mediated immunity, including cytotoxic T lymphocyte killing of infected cells, is critical to recovery from infection. Humoral immunity, including neutralizing antibody and antibody-dependent cell-mediated cytotoxicity, is important to prevention or control of (re-)infection. BHV-1 immune evasion strategies include suppression of major histocompatibility complex presentation of viral antigen, helper T-cell killing, and latency. Immune suppression caused by the virus potentiates secondary infections and contributes to the costly bovine respiratory disease complex. Vaccination against BHV-1 is widely practiced. The many vaccines reported include replicating and non-replicating, conventional and genetically engineered, as well as marker and non-marker preparations. Current development focuses on delivery of major BHV-1 glycoproteins to elicit a balanced, protective immune response, while excluding serologic markers and virulence or other undesirable factors. In North America, vaccines are used to prevent or reduce clinical signs, whereas in some European Union countries marker vaccines have been employed in the eradication of BHV-1 disease.

scholarly journals Infection of Cattle with a Bovine Herpesvirus 1 Strain That Contains a Mutation in the Latency-Related Gene Leads to Increased Apoptosis in Trigeminal Ganglia during the Transition from Acute Infection to Latency

2003 ◽  
Vol 77 (8) ◽  
pp. 4848-4857 ◽  
Author(s):  
Luciane Lovato ◽  
Melissa Inman ◽  
Gail Henderson ◽  
Alan Doster ◽  
Clinton Jones
Keyword(s):  
Nasal Cavity ◽  
Acute Infection ◽  
Bovine Herpesvirus ◽  
Pcr Analysis ◽  
Viral Gene ◽  
Trigeminal Ganglia ◽  
Dexamethasone Treatment ◽  
Bovine Herpesvirus 1 ◽  
Latently Infected ◽  
Herpesvirus 1

ABSTRACT Bovine herpesvirus 1 (BHV-1) is an important pathogen of cattle and infection is usually initiated via the ocular or nasal cavity. After acute infection, the primary site for BHV-1 latency is sensory neurons in the trigeminal ganglia (TG). Reactivation from latency occurs sporadically, resulting in virus shedding and transmission to uninfected cattle. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA. An LR mutant was constructed by inserting three stop codons near the beginning of the LR RNA. This mutant grows to wild-type (wt) efficiency in bovine kidney cells and in the nasal cavity of acutely infected calves. However, shedding of infectious virus from the eye and TG was dramatically reduced in calves infected with the LR mutant. Calves latently infected with the LR mutant do not reactivate after dexamethasone treatment. In contrast, all calves latently infected with wt BHV-1 or the LR rescued mutant reactivate from latency after dexamethasone treatment. In the present study, we compared the frequency of apoptosis in calves infected with the LR mutant to calves infected with wt BHV-1 because LR gene products inhibit apoptosis in transiently transfected cells. A sensitive TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay and an antibody that detects cleaved caspase-3 were used to identify apoptotic cells in TG. Both assays demonstrated that calves infected with the LR mutant for 14 days had higher levels of apoptosis in TG compared to calves infected with wt BHV-1 or to mock-infected calves. Viral gene expression, except for the LR gene, is extinguished by 14 days after infection, and thus this time frame is operationally defined as the establishment of latency. Real-time PCR analysis indicated that lower levels of viral DNA were present in the TG of calves infected with the LR mutant throughout acute infection. Taken together, these results suggest that the antiapoptotic properties of the LR gene play an important role during the establishment of latency.

scholarly journals CD4+ Cytotoxic T-Lymphocyte Activity against Macrophages Pulsed with Bovine Herpesvirus 1 Polypeptides

1998 ◽  
Vol 72 (9) ◽  
pp. 7040-7047 ◽  
Author(s):  
Chong Wang ◽  
Gary A. Splitter
Keyword(s):  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Cytotoxic T Lymphocyte ◽  
Bovine Herpesvirus ◽  
Target Cells ◽  
Peripheral Blood Mononuclear ◽  
Bovine Herpesvirus 1 ◽  
Effector Cells ◽  
Herpesvirus 1

ABSTRACT Bovine herpesvirus 1 (BHV-1) induces immune suppression, but the mechanisms for suppression are not well identified. We examined the induction and activity of BHV-1-specific cytolytic CD4+ T lymphocytes (CTL) by stimulating peripheral blood mononuclear cells (PBMC) of cattle immunized with attenuated live BHV-1. Cytolytic effector cells were primarily CD4+ T lymphocytes and lysed autologous, but not allogeneic, macrophages infected with BHV-1 or pulsed with BHV-1 polypeptides. Apoptosis of BHV-1-expressing target cells was observed in CD4+ CTL assays by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) analysis. To determine if apoptosis was mediated by a perforin- or Fas-mediated pathway, EGTA, a known selective inhibitor of the perforin pathway, was used. EGTA did not inhibit CD4+-T-cell-mediated cytotoxic activity, but it did limit the NK cell cytotoxicity of virus infected cells. These findings support the concept that CD4+ CTL lyse macrophages pulsed with BHV-1 polypeptides through a Fas-mediated lytic pathway by inducing apoptosis in the target cells. The prominent cytotoxicity mediated by CD4+ CTL suggests a mechanism of selective removal of viral antigen-associated antigen-presenting cells.

scholarly journals The Latency-Related Gene of Bovine Herpesvirus 1 Inhibits Programmed Cell Death

1999 ◽  
Vol 73 (12) ◽  
pp. 9734-9740 ◽  
Author(s):  
Janice Ciacci-Zanella ◽  
Melissa Stone ◽  
Gail Henderson ◽  
Clinton Jones
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Acute Infection ◽  
Bovine Herpesvirus ◽  
Productive Infection ◽  
Gene Products ◽  
Bovine Herpesvirus 1 ◽  
Transfected Cells ◽  
Herpesvirus 1

ABSTRACT Although viral gene expression occurs in the peripheral nervous system during acute infection, bovine herpesvirus 1 (BHV-1) gene expression is extinguished, many neurons survive, and latency ensues. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA, which is alternatively spliced in trigeminal ganglia during acute infection (L. Devireddy and C. Jones, J. Virol. 72:7294–7301, 1998). A subset of neurons express a protein encoded by the LR gene and the LR protein (LRP) is associated with cyclin-dependent kinase 2 (Cdk2)/cyclin complexes during productive infection (Y. Jiang, A. Hossain, M. T. Winkler, T. Holt, A. Doster, and C. Jones, J. Virol. 72:8133–8142, 1998). LR gene products inhibit cell cycle progression, perhaps as a result of LRP interacting with Cdk2/cyclin complexes. During acute infection, expression of cyclin A occurs in trigeminal ganglionic neurons (L. M. Schang, A. Hossain, and C. Jones, J. Virol. 70:3807–3814, 1996). Inappropriate expression of G1- and S-phase cyclins can initiate programmed cell death (PCD), apoptosis, in neurons, suggesting that LR gene products inhibit PCD. To test this hypothesis, we modified an assay to measure PCD frequency in transiently transfected cells. C6-ceramide, fumonisin B1(FB1), or etoposide was used to initiate PCD following transfection of cells with plasmids expressing LR gene products and the β-galactosidase gene. Transfected cells that survived were quantified by counting β-galactosidase-positive cells. Plasmids that expressed LR gene products promoted survival of monkey kidney (CV-1), human lung (IMR-90), or mouse neuroblastoma (neuro-2A) cells after induction of PCD. Plasmids with termination codons at the beginning of LR open reading frames or deletion of sequences that mediate splicing of LR RNA did not promote cell survival following PCD induction. We hypothesize that LR gene products play a role in promoting survival of postmitotic neurons during acute infection or reactivation.

Reverse immunogenetic and polyepitopic approaches for the induction of cell-mediated immunity against bovine viral pathogens

2000 ◽  
Vol 1 (2) ◽  
pp. 103-118 ◽  
Author(s):  
Nagendra R. Hegde ◽  
S. Srikumaran
Keyword(s):  
Infectious Diseases ◽  
Bovine Herpesvirus ◽  
Cell Mediated Immunity ◽  
Viral Pathogens ◽  
Bovine Herpesvirus 1 ◽  
The World ◽  
Herpesvirus 1 ◽  
Induced Immunity ◽  
Human And Mouse ◽  
Made In

AbstractThe control of several infectious diseases of animals by vaccination is perhaps the most outstanding accomplishment of veterinary medicine in the last century. Even the eradication of some pathogens is in sight, at least in some parts of the world. However, infectious diseases continue to cost millions of dollars to the livestock industry. One of the reasons for the failure to control certain pathogens is the limited emphasis placed on cell-mediated immunity (CMI) in the design of vaccines against these pathogens. Traditionally, vaccine-induced immunity has been studied in relation to antibody-mediated protection. More recent studies, however, have focused on understanding CMI and developing means of inducing CMI. This review focuses on recent advances made in the study of CMI in general and of cytotoxic T lymphocytes in particular. Parallels from studies in human and mouse immunology are drawn in order to point out implications to bovine immunology, specifically for immunity against bovine herpesvirus 1.

scholarly journals A Mutation in the Latency-Related Gene of Bovine Herpesvirus 1 Leads to Impaired Ocular Shedding in Acutely Infected Calves

2001 ◽  
Vol 75 (18) ◽  
pp. 8507-8515 ◽  
Author(s):  
Melissa Inman ◽  
Luciane Lovato ◽  
Alan Doster ◽  
Clinton Jones
Keyword(s):  
Nasal Cavity ◽  
Cell Cycle Progression ◽  
Clinical Symptoms ◽  
Acute Infection ◽  
Bovine Herpesvirus ◽  
Neutralizing Antibody ◽  
Gene Products ◽  
Viral Transcript ◽  
Bovine Herpesvirus 1 ◽  
Herpesvirus 1

ABSTRACT Bovine herpesvirus 1 (BHV-1) is an important pathogen of cattle, and infection is usually initiated in the ocular or nasal cavity. Like other alphaherpesviruses, BHV-1 establishes latency in sensory neurons but has the potential of reactivating from latency and spreading. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA, which is alternatively spliced in trigeminal ganglia during acute infection (L. R. Devireddy and C. Jones, J. Virol. 72:7294–7301, 1998). LR gene products inhibit cell cycle progression (Y. Jiang, A. Hossain, M. T. Winkler, T. Holt, A. Doster, and C. Jones, J. Virol. 72:8133–8142, 1998) and chemically induced apoptosis (J. Ciacci-Zannela, M. Stone, G. Henderson, and C. Jones. J. Virol. 73:9734–9740, 1999). Although these studies suggest that LR gene products play an important role in the latency/pathogenesis of BHV-1, construction of a mutant is necessary to test this hypothesis. Because the bICP0 gene overlaps and is antisense to the LR gene, it was necessary to mutate the LR gene without altering bICP0 expression. This was accomplished by inserting three stop codons near the beginning of the LR RNA, thus interfering with expression of proteins expressed by the LR RNA. The LR mutant virus grew with wild-type (WT) efficiency in bovine kidney (MDBK) cells and expressed bICP0 at least as efficiently as WT BHV-1 or the LR rescued virus. When calves were infected with the LR mutant, we observed a dramatic decrease (3 to 4 log units) in ocular shedding during acute infection relative to WT or the LR rescued virus. In contrast, shedding of the LR mutant from the nasal cavity was not significantly different from that of the WT or the LR rescued virus. Calves infected with the LR mutant exhibited mild clinical symptoms, but they seroconverted. Neutralizing antibody titers were lower in calves infected with the LR mutant, confirming reduced growth. In summary, this study suggests that an LR protein promotes ocular shedding during acute infection of calves.

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