Global S&T Development Trend Analysis Platform of Resources and Environment
The authors provide high-resolution structures of two arenavirus polymerases, revealing that the active site of arenavirus polymerase is inherently switched on, without the requirement for allosteric activation by 5 '
Arenaviruses can cause severe haemorrhagic fever and neurological diseases in humans and other animals, exemplified by Lassa mammarenavirus, Machupo mammarenavirus and lymphocytic choriomeningitis virus, posing great threats to public health(1-4). These viruses encode a large multi-domain RNA-dependent RNA polymerase for transcription and replication of the viral genome(5). Viral polymerases are one of the leading antiviral therapeutic targets. However, the structure of arenavirus polymerase is not yet known. Here we report the near-atomic resolution structures of Lassa and Machupo virus polymerases in both apo and promoter-bound forms. These structures display a similar overall architecture to influenza virus and bunyavirus polymerases but possess unique local features, including an arenavirus-specific insertion domain that regulates the polymerase activity. Notably, the ordered active site of arenavirus polymerase is inherently switched on, without the requirement for allosteric activation by 5 '
Sea-level histories during the two most recent deglacial-interglacial intervals show substantial differences(1-3) despite both periods undergoing similar changes in global mean temperature(4,5) and forcing from greenhouse gases(6). Although the last interglaciation (LIG) experienced stronger boreal summer insolation forcing than the present interglaciation(7), understanding why LIG global mean sea level may have been six to nine metres higher than today has proven particularly challenging(2). Extensive areas of polar ice sheets were grounded below sea level during both glacial and interglacial periods, with grounding lines and fringing ice shelves extending onto continental shelves(8). This suggests that oceanic forcing by subsurface warming may also have contributed to ice-sheet loss(9-12) analogous to ongoing changes in the Antarctic(13,14) and Greenland(15) ice sheets. Such forcing would have been especially effective during glacial periods, when the Atlantic Meridional Overturning Circulation (AMOC) experienced large variations on millennial timescales(16), with a reduction of the AMOC causing subsurface warming throughout much of the Atlantic basin(9,12,17). Here we show that greater subsurface warming induced by the longer period of reduced AMOC during the penultimate deglaciation can explain the more-rapid sea-level rise compared with the last deglaciation. This greater forcing also contributed to excess loss from the Greenland and Antarctic ice sheets during the LIG, causing global mean sea level to rise at least four metres above modern levels. When accounting for the combined influences of penultimate and LIG deglaciation on glacial isostatic adjustment, this excess loss of polar ice during the LIG can explain much of the relative sea level recorded by fossil coral reefs and speleothems at intermediate- and far-field sites.