JCI online early table of contents: April 8, 2008

In the study, TLR9 was shown to be essential for mice to mount protective immune responses against infection with the poxvirus that causes mousepox — ectromelia virus (ECTV). Indeed, TLR9-deficient mice succumbed to much lower doses of ECTV than did normal mice. By contrast, the strongly attenuated poxvirus modified vaccinia virus Ankara (MVA) induced both TLR9-dependent and TLR9-independent immune responses. It was then found that the ability of MVA to induce TLR9-independent immune responses could be harnessed to protect TLR9-deficient mice from infection with otherwise lethal doses of ECTV, even if the MVA was administered to the TLR9-deficient mice 2 days after they had been exposed to a lethal dose of ECTV. These data led the authors to suggest that administration of MVA might provide a useful immediate and therapeutic intervention against potentially fatal infection with a poxvirus in humans.

TITLE: Survival of lethal poxvirus infection in mice depends on TLR9, and therapeutic vaccination provides protection

AUTHOR CONTACT:

Hubertus Hochrein

Bavarian Nordic GmbH, Martinsried, Germany.

Phone: 49-89-8565-1334; Fax: 49-89-8565-1356; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33940

VIROLOGY

How immune cells get lost in chronic Hepatitis B infection

An immune response that successfully clears an infection with Hepatitis B virus (HBV) includes CD8+ T cells that specifically target cells infected with HBV. The number of these cells is markedly diminished in individuals that fail to clear HBV and become chronically (persistently) infected with the virus. New insight into the mechanisms underlying the decreased number of HBV-specific CD8+ T cells in individuals chronically infected with HBV has now been provided by Mala Maini and colleagues, at University College London, United Kingdom.

In the study, it was found that HBV-specific CD8+ T cells from individuals who had successfully cleared an HBV infection and from individuals chronically infected with HBV expressed different patterns of genes. Specifically, HBV-specific CD8+ T cells from individuals chronically infected with HBV expressed large numbers of genes containing the information for making proteins involved in a form of cell death known as apoptosis. Detailed analysis indicated that CD8+ T cells from individuals chronically infected with HBV expressed the proapoptotic protein Bim and that blocking Bim-mediated apoptosis increased the number of HBV-specific CD8+ T cells both in culture and directly ex vivo. The authors therefore suggest that Bim-mediated apoptosis of HBV-specific CD8+ T cells contributes to the inability of these cells to persist and clear virus in individuals chronically infected with HBV.

TITLE: Bim-mediated deletion of antigen-specific CD8+ T cells in patients unable to control HBV infection

AUTHOR CONTACT:

Mala K. Maini

University College London, London, United Kingdom.

Phone: 44-0-20-7679-9212; Fax: 44-0-20-7679-9652; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33402