scholarly journals Vaccinia Virus Infection Disarms the Mitochondrion-Mediated Pathway of the Apoptotic Cascade by Modulating the Permeability Transition Pore

2001 ◽  
Vol 75 (23) ◽  
pp. 11437-11448 ◽  
Author(s):  
Shawn T. Wasilenko ◽  
Adrienne F. A. Meyers ◽  
Kathleen Vander Helm ◽  
Michele Barry
Keyword(s):  
Virus Infection ◽  
Vaccinia Virus ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Jurkat Cells ◽  
Caspase 8 ◽  
Apoptotic Pathway ◽  
Vaccinia Virus Infection ◽  
Infected Cells ◽  
Apoptotic Cascade

ABSTRACT Many viruses have evolved strategies that target crucial components within the apoptotic cascade. One of the best studied is the caspase 8 inhibitor, crmA/Spi-2, encoded by members of the poxvirus family. Since many proapoptotic stimuli induce apoptosis through a mitochondrion-dependent, caspase 8-independent pathway, we hypothesized that vaccinia virus would encode a mechanism to directly modulate the mitochondrial apoptotic pathway. In support of this, we observed that Jurkat cells, which undergo Fas-mediated apoptosis exclusively through the mitochondrial route, were resistant to Fas-induced death following infection with a crmA/Spi-2-deficient strain of vaccinia virus. In addition, vaccinia virus-infected cells subjected to the proapoptotic stimulus staurosporine exhibited decreased levels of both cytochromec released from the mitochondria and caspase 3 activation. In all cases we found that the loss of the mitochondrial membrane potential, which occurs as a result of opening the multimeric permeability transition pore complex, was prevented in vaccinia virus-infected cells. Moreover, vaccinia virus infection specifically inhibited opening of the permeability transition pore following treatment with the permeability transition pore ligand atractyloside and t-butylhydroperoxide. These studies indicate that vaccinia virus infection directly impacts the mitochondrial apoptotic cascade by influencing the permeability transition pore.

scholarly journals Recognition of Vaccinia Virus-Infected Cells by Human Natural Killer Cells Depends on Natural Cytotoxicity Receptors

2006 ◽  
Vol 80 (5) ◽  
pp. 2225-2233 ◽  
Author(s):  
Susan E. Chisholm ◽  
Hugh T. Reyburn
Keyword(s):  
Virus Infection ◽  
Vaccinia Virus ◽  
Nk Cells ◽  
Natural Killer ◽  
Target Cell ◽  
Target Cells ◽  
Natural Cytotoxicity ◽  
Vaccinia Virus Infection ◽  
Infected Cells ◽  
Natural Cytotoxicity Receptors

ABSTRACT Natural Killer (NK) cells are important in the immune response to a number of viruses; however, the mechanisms used by NK cells to discriminate between healthy and virus-infected cells are only beginning to be understood. Infection with vaccinia virus provokes a marked increase in the susceptibility of target cells to lysis by NK cells, and we show that recognition of the changes in the target cell induced by vaccinia virus infection depends on the natural cytotoxicity receptors NKp30, NKp44, and NKp46. Vaccinia virus infection does not induce expression of ligands for the activating NKG2D receptor, nor does downregulation of major histocompatibility complex class I molecules appear to be of critical importance for altered target cell susceptibility to NK cell lysis. The increased susceptibility to lysis by NK cells triggered upon poxvirus infection depends on a viral gene, or genes, transcribed early in the viral life cycle and present in multiple distinct orthopoxviruses. The more general implications of these data for the processes of innate immune recognition are discussed.

scholarly journals Vaccinia Virus Infection Attenuates Innate Immune Responses and Antigen Presentation by Epidermal Dendritic Cells

2006 ◽  
Vol 80 (20) ◽  
pp. 9977-9987 ◽  
Author(s):  
Liang Deng ◽  
Peihong Dai ◽  
Wanhong Ding ◽  
Richard D. Granstein ◽  
Stewart Shuman
Keyword(s):  
Virus Infection ◽  
Vaccinia Virus ◽  
Poly I:C ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Vaccinia Virus Infection ◽  
Tnf Α ◽  
Infected Cells ◽  
Virus Mutant

ABSTRACT Langerhans cells (LCs) are antigen-presenting cells in the skin that play sentinel roles in host immune defense by secreting proinflammatory molecules and activating T cells. Here we studied the interaction of vaccinia virus with XS52 cells, a murine epidermis-derived dendritic cell line that serves as a surrogate model for LCs. We found that vaccinia virus productively infects XS52 cells, yet this infection displays an atypical response to anti-poxvirus agents. Whereas adenosine N1-oxide blocked virus production and viral protein synthesis during a synchronous infection, cytosine arabinoside had no effect at concentrations sufficient to prevent virus replication in BSC40 monkey kidney cells. Vaccinia virus infection of XS52 cells not only failed to elicit the production of various cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, IL-12 p40, alpha interferon (IFN-α), and IFN-γ, it actively inhibited the production of proinflammatory cytokines TNF-α and IL-6 by XS52 cells in response to exogenous lipopolysaccharide (LPS) or poly(I:C). Infection with a vaccinia virus mutant lacking the E3L gene resulted in TNF-α secretion in the absence of applied stimuli. Infection of XS52 cells or BSC40 cells with the ΔE3L virus, but not wild-type vaccinia virus, triggered proteolytic decay of IκBα. These results suggest a novel role for the E3L protein as an antagonist of the NF-κB signaling pathway. ΔE3L-infected XS52 cells secreted higher levels of TNF-α and IL-6 in response to LPS and poly(I:C) than did cells infected with the wild-type virus. XS52 cells were productively infected by a vaccinia virus mutant lacking the K1L gene. ΔK1L-infected cells secreted higher levels of TNF-α and IL-6 in response to LPS than wild-type virus-infected cells. Vaccinia virus infection of primary LCs harvested from mouse epidermis was nonpermissive, although a viral reporter protein was expressed in the infected LCs. Vaccinia virus infection of primary LCs strongly inhibited their capacity for antigen-specific activation of T cells. Our results highlight suppression of the skin immune response as a feature of orthopoxvirus infection.

scholarly journals Role of the Mitochondrial Signaling Pathway in Murine Coronavirus-Induced Oligodendrocyte Apoptosis

2006 ◽  
Vol 80 (1) ◽  
pp. 395-403 ◽  
Author(s):  
Yin Liu ◽  
Yinghui Pu ◽  
Xuming Zhang
Keyword(s):  
Hepatitis Virus ◽  
Mitochondrial Pathway ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Antiapoptotic Proteins ◽  
Mitochondrial Signaling ◽  
Drastic Increase ◽  
Infected Cells

ABSTRACT A previous study demonstrated that infection of rat oligodendrocytes by mouse hepatitis virus (MHV) resulted in apoptosis, which is caspase dependent (Y. Liu, Y. Cai, and X. Zhang, J. Virol. 77:11952-11963, 2003). Here we determined the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis. We found that caspase-9 activity was 12-fold higher in virus-infected cells than in mock-infected cells at 24 h postinfection (p.i.). Pretreatment of cells with a caspase-9 inhibitor completely blocked caspase-9 activation and partially inhibited the apoptosis mediated by MHV infection. Analyses of cytochrome c release further revealed an activation of the mitochondrial apoptotic pathway. Stable overexpression of the two antiapoptotic proteins Bcl-2 and Bcl-xL significantly, though only partially, blocked apoptosis, suggesting that activation of the mitochondrial pathway is partially responsible for the apoptosis. To identify upstream signals, we determined caspase-8 activity, cleavage of Bid, and expression of Bax and Bad by Western blotting. We found a drastic increase in caspase-8 activity and cleavage of Bid at 24 h p.i. in virus-infected cells, suggesting that Bid may serve as a messenger to relay the signals from caspase-8 to mitochondria. However, treatment with a caspase-8 inhibitor only slightly blocked cytochrome c release from the mitochondria. Furthermore, we found that Bax but not Bad was significantly increased at 12 h p.i. in cells infected with both live and UV-inactivated viruses and that Bax activation was partially blocked by treatment with the caspase-8 inhibitor. These results thus establish the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis.

scholarly journals Vaccinia Virus Infection in Monkeys, Brazilian Amazon

2010 ◽  
Vol 16 (6) ◽  
pp. 976-979 ◽  
Author(s):  
Jônatas S. Abrahão ◽  
André T. Silva-Fernandes ◽  
Larissa S. Lima ◽  
Rafael K. Campos ◽  
Maria I.M.C. Guedes ◽  
...  
Keyword(s):  
Virus Infection ◽  
Vaccinia Virus ◽  
Brazilian Amazon ◽  
Vaccinia Virus Infection

H–2-like specificities of foreign haplotypes appearing on a mouse sarcoma after vaccinia virus infection

Nature ◽  
1976 ◽  
Vol 259 (5540) ◽  
pp. 228-230 ◽  
Author(s):  
FEDERICO GARRIDO ◽  
VOLKER SCHIRRMACHER ◽  
HILLIARD FESTENSTEIN
Keyword(s):  
Virus Infection ◽  
Vaccinia Virus ◽  
Vaccinia Virus Infection ◽  
Mouse Sarcoma

scholarly journals 1207. Vaccinia Virus Infection Acquired from an Occupational Needlestick—San Diego, California, 2019

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S434-S434
Author(s):  
Erin R Whitehouse ◽  
Agam Rao ◽  
Yon Yu ◽  
Patricia Yu ◽  
Margaret Griffin ◽  
...  
Keyword(s):  
Virus Infection ◽  
Vaccinia Virus ◽  
Treatment Decisions ◽  
Left Index Finger ◽  
Severe Illness ◽  
Local Health ◽  
Health Clinics ◽  
Vaccinia Virus Infection ◽  
Medication Access ◽  
Specific Strain

Abstract Background Vaccinia virus, a virus similar to but less virulent than variola virus, is a component of smallpox vaccines and increasingly used for medical research. Vaccinia immunoglobulin intravenous (VIGIV) and tecovirimat are stockpiled in the U.S. Strategic National Stockpile (SNS) for potential smallpox bioterror events, but only VIGIV is licensed for vaccinia treatment. On January 12, 2019, CDC was consulted for worsening infection in a laboratory worker after a needlestick with vaccinia. Methods We investigated demographic, clinical, vaccination, and exposure history and determined likelihood of vaccinia virus infection. Identity of the specific strain was sought because some have genetic modifications that might impact virulence. Discussions among stakeholders informed treatment decisions and facilitated medication access and usage. Swabs from the lesion were tested by real-time polymerase chain reaction for orthopoxvirus DNA, which includes vaccinia. Results The affected worker was an otherwise healthy 26-year-old woman who developed a pustular lesion at the needlestick site on her left index finger (Image). The patient had been injecting vaccinia virus into a mouse and had declined nationally recommended vaccination. Edema, lymphadenopathy, and fever raised concern for severe illness; neither the patient nor occupational health were certain of the vaccinia strain type. CDC, SNS, local health departments, drug manufacturers, and clinicians rapidly collaborated to make treatment decisions based on available information and ensure delivery of both biologics and administration of tecovirimat under an expanded access investigational new drug protocol. Eventually, a wound swab tested positive and the strain was determined to be one with no known impact on virulence. Conclusion With increasing use of vaccinia in research, occupational infections may continue to occur. Health clinics should extensively counsel staff who decline vaccination and have documentation on-hand about vaccinia virus types to inform treatment decisions. This response prompted CDC to develop outreach materials specifically for occupational vaccinia exposures. Disclosures All authors: No reported disclosures.

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