Volume 540 Number 7633

Editorials

News

News Features

News & Views

Inside-out receptor inhibition p.344

Structures of two chemokine receptor proteins in complex with small molecules reveal a previously unknown binding pocket that could be a drug target for treating a range of diseases involving this receptor family. See Letters p.458 & p.462

doi: 10.1038/nature20486

A radical change in enzyme catalysis p.345

A method has been devised that allows a ketoreductase enzyme to catalyse reactions other than its natural ones. The key is to excite the enzyme's cofactor using light – an approach that might work for other enzymes. See Letter p.414

doi: 10.1038/540345a

A gene-expression profile for leukaemia p.346

Can simple genetic risk profiles be identified for complex diseases? The development of a gene-expression profile for acute myeloid leukaemia suggests that they can, and that they may improve prognosis prediction. See Letter p.433

doi: 10.1038/nature20488

The dynamics of Earth's surface water p.348

High-resolution satellite mapping of Earth's surface water during the past 32 years reveals changes in the planet's water systems, including the influence of natural cycles and human activities. See Letter p.418

doi: 10.1038/nature21100

Cause and consequence in aged-muscle decline p.349

Activation of aged muscle stem cells induces changes in DNA packaging that lead to expression of the gene Hoxa9. This reactivates embryonic signalling pathways, restricting the cells' ability to repair injured muscle. See Letter p.428

doi: 10.1038/nature20485

An eye on retinal recovery p.350

Retinal-cell transplants restore vision in mouse models of retinal degeneration. It emerges that the transplant leads to an exchange of material between donor and host cells — not to donor-cell integration into the retina, as had been presumed.

doi: 10.1038/nature20487

Articles

Electric-field-stimulated protein mechanics p.400

A new method in which strong electric fields are applied to a protein crystal while collecting time-resolved X-ray diffraction patterns is able to follow the mechanical motions of all the constituent atoms, with implications for molecular biology and drug discovery.

doi: 10.1038/nature20571

Letters

Zika virus infection damages the testes in mice p.438

Infection of male mice with Zika virus caused testicular and epididymal damage, reduction in sex hormone levels, destruction of germ and somatic cells in the testis, loss of mature sperm and reduction in fertility.

doi: 10.1038/nature20556

Receptor usage dictates HIV-1 restriction by human TRIM5α in dendritic cell subsets p.448

The most prevalent route of HIV-1 infection is across mucosal tissues after sexual contact. Langerhans cells (LCs) belong to the subset of dendritic cells (DCs) that line the mucosal epithelia of vagina and foreskin and have the ability to sense and induce immunity to invading pathogens. Anatomical and functional characteristics make LCs one of the primary targets of HIV-1 infection. Notably, LCs form a protective barrier against HIV-1 infection and transmission. LCs restrict HIV-1 infection through the capture of HIV-1 by the C-type lectin receptor Langerin and subsequent internalization into Birbeck granules. However, the underlying molecular mechanism of HIV-1 restriction in LCs remains unknown. Here we show that human E3-ubiquitin ligase tri-partite-containing motif 5α (TRIM5α) potently restricts HIV-1 infection of LCs but not of subepithelial DC-SIGN+ DCs. HIV-1 restriction by TRIM5α was thus far considered to be reserved to non-human primate TRIM5α orthologues, but our data strongly suggest that human TRIM5α is a cell-specific restriction factor dependent on C-type lectin receptor function. Our findings highlight the importance of HIV-1 binding to Langerin for the routeing of HIV-1 into the human TRIM5α-mediated restriction pathway. TRIM5α mediates the assembly of an autophagy-activating scaffold to Langerin, which targets HIV-1 for autophagic degradation and prevents infection of LCs. By contrast, HIV-1 binding to DC-SIGN+ DCs leads to disassociation of TRIM5α from DC-SIGN, which abrogates TRIM5α restriction. Thus, our data strongly suggest that restriction by human TRIM5α is controlled by C-type-lectin-receptor-dependent uptake of HIV-1, dictating protection or infection of human DC subsets. Therapeutic interventions that incorporate C-type lectin receptors and autophagy-targeting strategies could thus provide cell-mediated resistance to HIV-1 in humans.

doi: 10.1038/nature20567