PMC:3463543 / 1854-5269
Annnotations
2_test
{"project":"2_test","denotations":[{"id":"23056454-16574822-92972522","span":{"begin":149,"end":150},"obj":"16574822"},{"id":"23056454-17369609-92972523","span":{"begin":154,"end":155},"obj":"17369609"},{"id":"23056454-11289677-92972524","span":{"begin":256,"end":257},"obj":"11289677"},{"id":"23056454-19556586-92972525","span":{"begin":260,"end":261},"obj":"19556586"},{"id":"23056454-15557003-92972526","span":{"begin":441,"end":442},"obj":"15557003"},{"id":"23056454-21097384-92972527","span":{"begin":446,"end":447},"obj":"21097384"},{"id":"23056454-13713229-92972528","span":{"begin":534,"end":535},"obj":"13713229"},{"id":"23056454-19204283-92972529","span":{"begin":539,"end":540},"obj":"19204283"},{"id":"23056454-20186267-92972530","span":{"begin":651,"end":653},"obj":"20186267"},{"id":"23056454-20872724-92972531","span":{"begin":656,"end":658},"obj":"20872724"},{"id":"23056454-13713229-92972532","span":{"begin":807,"end":808},"obj":"13713229"},{"id":"23056454-13904777-92972533","span":{"begin":812,"end":814},"obj":"13904777"},{"id":"23056454-14774528-92972534","span":{"begin":817,"end":819},"obj":"14774528"},{"id":"23056454-21097384-92972535","span":{"begin":1247,"end":1248},"obj":"21097384"},{"id":"23056454-13713229-92972536","span":{"begin":1304,"end":1305},"obj":"13713229"},{"id":"23056454-13904777-92972537","span":{"begin":1319,"end":1321},"obj":"13904777"},{"id":"23056454-14774528-92972538","span":{"begin":1434,"end":1436},"obj":"14774528"},{"id":"23056454-987765-92972539","span":{"begin":1459,"end":1461},"obj":"987765"},{"id":"23056454-19204283-92972540","span":{"begin":1826,"end":1827},"obj":"19204283"},{"id":"23056454-21731764-92972541","span":{"begin":1979,"end":1981},"obj":"21731764"},{"id":"23056454-19081209-92972542","span":{"begin":2299,"end":2301},"obj":"19081209"},{"id":"23056454-11874811-92972543","span":{"begin":2607,"end":2609},"obj":"11874811"},{"id":"23056454-2681268-92972544","span":{"begin":2613,"end":2615},"obj":"2681268"}],"text":"Introduction\nInfluenza has distinct transmission patterns around the world. In temperate regions, influenza’s incidence peaks during the wintertime [1], [2], while in some tropical regions, the disease’s occurrence seems to coincide with the rainy season [3]–[5]. These patterns have triggered intense interest in unveiling the mechanisms behind them. However, a consistent explanation is lacking, despite nearly a century of investigation [6], [7].\nHumidity has been identified as one factor that influences influenza’s seasonality [8], [9]. Previous studies have linked influenza’s high incidence in temperate regions to low humidity in wintertime [10]–[12]. This connection is further supported by laboratory studies indicating that influenza A virus (IAV) survives better at low relative humidity (RH) [8], [13]–[15].\nNevertheless, several important questions remain to be addressed. Firstly, the connection between high influenza incidence and low humidity fails to explain increased influenza activity in some tropical areas during the rainy season when humidity is maximal. Secondly, although laboratory studies consistently showed a high survival rate for IAV at low RH (\u003c50%), results were discordant at medium to high (∼50% to ∼90%) RH [7]. Of the four studies cited most often, Hemmes et al. [8] and Harper [13] (referred to as H\u0026H hereafter) found higher inactivation rates at both medium and high RH, while Shechmeister [15] and Schaffer et al. [14] (referred to as S\u0026S hereafter) reported the highest inactivation rates at medium RH and moderate ones at high RH. The relationship between the viability of IAV in airborne droplets and ambient RH remains poorly defined and poorly understood.\nAnother unanswered question surrounds the mechanism by which humidity might affect IAV in airborne respiratory droplets [9]. After release from the respiratory tract, where RH is ∼100%, a respiratory droplet shrinks by 40–50% in diameter at RH below 90% due to evaporation [16]–[18]. As a result, concentrations of solutes in the droplet increase by up to 15 times, and solutes such as salts (e.g., sodium chloride (NaCl)) that are harmless at physiological levels may become harmful to the virus. For example, avian IAV has been reported to be less stable at salinities greater than 25 g L−1 [19]. Evaporation induces changes to IAV’s microenvironment inside droplets that may affect the virus’ viability, and the toxic effect of solutes may be enhanced at lower RH due to higher concentrations that result from greater loss of water. However, respiratory droplets also contain a variety of proteins [20], [21], and their interactions with salts at different RHs may complicate this picture under natural conditions.\nWe hypothesize that humidity mediates the survival of IAV in a droplet by controlling the extent of evaporation and thus solute concentrations in the droplet and that solute concentrations in the droplet define the relationship between RH and IAV viability. We designed a simple experiment to test the effects of salts and proteins on the viability of IAV and, for the first time, to determine its relationship with RH in human mucus. Our results resolve the aforementioned discrepancy in the literature. Based on these results, we propose a mechanistic explanation for the dependence of IAV’s survival on humidity and influenza’s transmission patterns in both temperate and tropical regions."}