Priming of immature thymocytes to CD3-mediated apoptosis by infection with murine cytomegalovirus

An avirulent mutant of Sendai virus, Ohita-MVC11 (MVC11), was generated from a highly virulent field strain, Ohita-M1 (M1), through successive passages in LLC-MK2 cell cultures (M. Itoh, Y. Isegawa, H. Hotta, and M. Homma, J. Gen. Virol. 78:3207-3215, 1997). In LLC-MK2 cells, MVC11 induced a high degree of apoptotic cell death that was demonstrated by chromatin condensation of the nucleus and DNA fragmentation, and production of MVC11 declined markedly after prolonged culture. On the other hand, M1 did not induce prominent apoptosis and maintained high virus titers. In primary mouse pulmonary epithelial cell cultures, M1 replicated rather slowly to reach maximum level of virus production at 3 days postinfection, and high levels of virus production were maintained thereafter without causing apoptosis. In contrast, MVC11, which produced 20 times more progeny virus than M1 at 1 day postinfection, induced a high degree of apoptotic cell death before the virus replication cycle was completed. Accordingly, the production of progeny virus was strongly inhibited thereafter. In the lungs of mice infected with MVC11, virus antigens and signals of DNA fragmentation detected by the in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling technique colocalized in bronchial epithelial cells, clearly demonstrating that infection by MVC11 triggered apoptosis in vivo as well as in vitro. These results suggest the possibility that induction of apoptosis by MVC11 plays an important role in attenuation of mouse pathogenicity by restricting progeny virus production in the lung. The C protein was shown to have the capacity to induce apoptosis, and the increased level of the C protein in MVC11-infected cells was considered to account partly, if not entirely, for the induction of apoptosis.

Section: Discussionmentioning

confidence: 99%

Increased Induction of Apoptosis by a Sendai Virus Mutant Is Associated with Attenuation of Mouse Pathogenicity

Itoh

Hotta

Homma

1998

“…Furthermore, apoptosis has been implicated as a mechanism of cell damage in response to DEN virus replication in vitro (10). Several viruses have been shown to induce programmed cell death (apoptosis), which often contributes directly to their cytopathogenic effects in host cells (see for a review, see reference 51) (12,28,30,35,42,51,56). This led us to investigate whether apoptotic cell death of human hepatoma cells was triggered by DEN-1 virus infection.…”

Section: The Severe Outcome Of the Dengue (Den) Virus Infection Knownmentioning

confidence: 99%

Dengue virus replication in human hepatoma cells activates NF-kappaB which in turn induces apoptotic cell death

Marianneau

Cardona

Edelman

et al. 1997

190

The severe outcome of the dengue (DEN) virus infection known as DEN hemorrhagic fever-DEN shock syndrome (DHF-DSS) is, in some cases, accompanied by liver injury. Councilman bodies observed in liver biopsies of DHF-DSS cases may correspond to hepatocytes in apoptosis. We show here that infection of the hepatoma cell line HepG2 with DEN type 1 virus induced cell death typical of apoptosis late in the virus cycle. The transcription factor NF-kappaB was activated concomitantly with viral protein synthesis and thus before the appearance of apoptotic cells. Inhibition of apoptosis was observed when DEN virus-infected cells were treated with NF-kappaB decoys, indicating the involvement of this transcription factor in induction of cell death. Thus, infected hepatocytes appear to be subject to apoptosis in vitro, and this may be a key element in the pathophysiology of hepatic failure associated with DHF-DSS.

“…Infection of cultured cells with a wide variety of viruses, including herpesviruses (22,25,26,28), parvoviruses (38), retroviruses (9,30,36,39,41), paramyxoviruses (8), myxoviruses (12,20,42), alphaviruses (33,49), and picornaviruses (44), results in activation of a programmed cell death pathway. This built-in cell suicide program is required for normal embryonic development and tissue homeostasis and may also be an important host defense mechanism to eliminate virus-infected cells (27).…”

mentioning

confidence: 99%

Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence

Lewis

Wesselingh

Griffin

et al. 1996

214

Sindbis virus induces apoptotic cell death in cultured cell lines, raising the possibility that apoptosis of infected neurons and other target cells in vivo may contribute to the resulting disease and mortality. To investigate the role of apoptosis in Sindbis virus pathogenesis, infected mouse brains were assayed by the in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling technique and for DNA ladder formation. Infection with recombinant Sindbis virus strain 633 resulted in widespread apoptosis in newborn mouse brains and spinal cords, but few apoptotic cells were observed following infection of 2-week-old animals. This finding correlates with the age-dependent mortality observed in mice. The more neurovirulent virus TE, which differs from 633 by a single amino acid in the E2 glycoprotein, induced significant apoptosis in brains and spinal cords of 2-week-old animals, consistent with its ability to cause fatal disease in older animals. Double-labeling experiments demonstrated that the apoptotic cells were also infected with Sindbis virus. Thus, Sindbis virus-induced apoptosis appears to be a direct result of virus infection and is likely to reflect pathogenic mechanisms for other viruses.