Viral immunity

APOBEC-mediated editing of viral RNA. Bishop, K. N. et al. Science 305, 645 (2004).

A flurry of recent papers have described the retroviral-restriction activity of APOBEC proteins — notably, APOBEC3F and APOBEC3G — involving deamination of minus-strand viral cDNAs. This paper now describes that APOBEC1 can deaminate viral RNA, which extends the role of APOBEC-family members in innate resistance to viral infection to both DNA and RNA deamination. Rat APOBEC1 caused an accumulation of cytosine-to-uracil changes in HIV genomic RNA, indicating that it might have a role in inducing mutations in viruses that replicate entirely through RNA. Also, because APOBEC1 is already known to deaminate a particular cytosine residue in apolipoprotein B mRNA, this demonstration of viral RNA editing might indicate that there are also other cellular RNA substrates for APOBEC1.

T-cell signalling

Discs large (Dlg1) complexes in lymphocyte activation. Xavier, R. et al. J. Cell Biol. 165, 173–178 (2004).

When a T cell encounters another cell presenting its cognate antigen, an immunological synapse forms at the interface between the two cells. It is still unclear how the cytoskeletal changes required for synapse formation are coordinated with signalling as a result of antigen recognition, but this study shows that the PDZ-domain-containing protein Discs large 1 (Dlg1) is involved. PDZ domains can support heterotypic and homotypic interactions, making proteins that contain them ideal scaffolding molecules. Indeed, Dlg1 is already known to be expressed at synapses between neurons in the central nervous system. In T cells, the authors show that Dlg1 is recruited with actin to the contact zone with an antigen-presenting cell, and it also associates with T-cell signalling molecules such as LCK. Dlg1 seems to inhibit signalling from the synapse: overexpression of the protein attenuated VAV1-induced transcription activity, whereas Dlg1 suppression potentiated the response to stimulation through CD3.

Phagocytosis

Dectin-1 utilizes novel mechanisms for yeast phagocytosis in macrophages. Herre, J. et al. Blood 10 August 2004 (doi:1182/blood-2004-03-1140).

The C-type lectin-like receptor Dectin-1 is required for the inflammatory response to β-glucans, such as those found in fungal pathogens. In this study, Dectin-1 is shown to mediate another process crucial for host defence — phagocytosis. Dectin-1-mediated internalization of the yeast particle zymosan required an ITAM-like motif in its cytoplasmic tail similar to the ITAM sequence required for FcγR-mediated phagocytosis. However, Dectin-1-mediated uptake involved a different combination of signalling molecules than FcγR-mediated phagocytosis or than used by other phagocytic receptors previously studied. Furthermore, when considering the biological importance of Dectin-1-mediated phagocytosis, it should be noted that its route of intracellular trafficking was dependent on the nature of the β-glucan ligand.