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NATURE REVIEWS | IMMUNOLOGY VOLUME 3 | SEPTEMBER 2003 | 695

Viruses are always striving to outwittheir host, and staying one stepahead is proving difficult in ourfight against HIV-1. The expressionof inhibitors, known as restrictionfactors, by humans and nonhumanprimates provides an innatemechanism that confers resistanceto infection with variousretroviruses. However, it seems thatHIV-1 can hijack a host protein tocounteract the inhibition of virusreplication mediated by thesefactors. Reporting in NatureMedicine, Towers et al. show thatthe interaction between HIV-1capsid protein (CA) and the hostcell protein cyclophilin A (CYPA)modulates the sensitivity of HIV-1to host restriction factors.

The CYPA binding site in CA ispositioned close to residues that areinvolved in recognition byrestriction factors. So, the authorsinvestigated how the interactionbetween CA and CYPA influencesthe sensitivity of HIV-1 torestriction factors. Disruption ofthe CYPA−CA interaction either by

mutating the CYPA binding site inHIV-1 CA or by treating the targetcells with cyclosporin A (CsA),which effectively competes for the binding of CYPA, had differenteffects on HIV-1 infectivitydepending on the species of thetarget cell. In human cells, inhibitionof the CYPA−CA interactionreduced the infectivity of HIV-1,as HIV-1 became sensitive to therestriction factor REF1. By contrast,efficient infection of owl monkey(OMK) cells occurred when theCYPA−CA interaction wasprevented, indicating that thisbinding event is required forrestriction by OMK cells.

Therefore, it seems that specificadaptation of HIV-1 in humancells, but not unnatural hosts, hasallowed HIV-1 to avoid recognitionby restriction factors and overrideinnate antiviral safety measures.

Lucy Bird

References and linksORIGINAL RESEARCH PAPER Towers, G. J.et al. Cyclophilin A modulates the sensitivity ofHIV-1 to host restriction factors. Nature Med. 3 August 2003 (DOI: 10.1038/nm910)

Overriding safetymeasures

H I V IN BRIEF

AID mutant analyses indicate requirement for class-switch-specific cofactors.Ta, V.-T. et al. Nature Immunol. 10 August 2003 (DOI: 10.1038/ni964)

Activation-induced cytidine deaminase (AID) is known to be the only B-cell-specific factor required for both class-switchrecombination (CSR) and somatic hypermutation (SHM) duringthe maturation of an antibody response. How then does AIDdifferentially regulate these two processes? Honjo and colleaguesshow that this might be achieved by specific cofactors thatregulate substrate interaction. Point mutations in the carboxy-terminal domain of AID abrogated CSR but did not affect SHM,which indicates the involvement of a CSR-specific cofactor thatbinds to the carboxyl terminus of AID.

The nonimmunoglobulin portion of λ5 mediates cell-autonomous pre-B cell receptor signaling.Ohnishi, K. & Melchers, F. Nature Immunol. 3 August 2003 (DOI: 10.1038/ni959)

Expression of the pre-BCR — composed of one rearranged heavychain and a surrogate light chain (SLC; which is itself composedof VpreB and λ5) — is a crucial intermediate step in B-celldevelopment, allowing B cells to proliferate in a ligand-independentmanner. Deletion or mutation of the amino-terminal non-immunoglobulin region of λ5 led to increased cell-surfaceexpression of the pre-BCR, but decreased pre-BCR aggregation anddecreased phosphorylation of proteins in the pre-BCR complex.These results indicate that the amino-terminal region of λ5 isrequired for signal transduction by the pre-BCR in response toreceptor crosslinking. No ligands or other cell types were added tothe pre-B cells, so the authors propose that this crosslinking involvesa linking factor produced by the pre-B cell itself or non-covalentinteractions between two λ5 non-immunoglobulin regions.

Cutting edge: the B cell chemokine CXC chemokineligand 13/B lymphocyte chemoattractant is expressedin the high endothelial venules of lymph nodes andPeyer’s patches and affects B cell trafficking acrosshigh endothelial venules.Ebisuno, Y. et al. J. Immunol. 171, 1642–1646 (2003)

The chemokines CC-chemokine ligand 21 (CCL21) and CCL19are localized to high endothelial venules (HEVs) and are involvedin controlling T-cell trafficking to lymph nodes or Peyer’spatches. In this study, Ebisuno et al. analysed the role of the B-cellchemoattractant CXCL13 in the trafficking of B cells across HEVs.CXCL13 was found to be expressed on the luminal surface of HEVs.B-cell arrest in HEVs of Peyer’s patches was impaired in CXCL13-deficient mice, but superfusion of the Peyer’s patches with CXCL13restored the expression of CXCL13 at the luminal surface and someB cells were once again able to adhere. This study shows thatCXCL13 expressed by HEVs has a role in the trafficking of B cells in lymphoid organs.

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