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Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, its local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. While we did not find that transmission dynamics in Basel correlate with humidity or school closures, we did find some evidence that it may positively correlated with temperature. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the elderly were to a large extent infected within their own transmission network. In the remaining transmission network, our analyses suggest that school-aged children likely play a more central role than pre-school aged children. These patterns will be valuable to plan interventions combating the spread of respiratory diseases within cities given that similar patterns are observed for other influenza seasons and cities., Author Summary As shown with the current SARS-CoV-2 pandemic, respiratory diseases can quickly spread around the globe. While it can be important to understand how diseases spread around the globe, local spread is most often the main driver of novel infections of respiratory diseases such as SARS-CoV-2 or influenza. We here use genetic sequence data alongside patient information to better understand what drives the local spread of influenza by looking at the 2016/2017 influenza season in Basel, Switzerland as an example. The genetic sequence data allows us to reconstruct how the transmission dynamics changed over the course of the season, which we then compare to trends in humidity and temperature and times when schools were open or closed. Additionally, the genetic sequence data allows us to see how individual cases are connected. Using patient information, such as age and household status our analyses suggest that the elderly mainly transmit within their own transmission network. Additionally, they suggest that school aged children, but not necessarily pre-school aged children are important drivers of the local spread of influenza.

Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses., Author Summary How quickly infection occurs should be an important determinant of viral fitness, but mechanisms which could accelerate the onset of viral gene expression were previously undefined. In this work we use time-lapse microscopy to quantify the timing of the HIV viral cycle and show that onset of viral gene expression can be substantially accelerated. This occurs during cell-to-cell spread of HIV, a mode of directed viral infection where multiple virions are transmitted between cells. Surprisingly, we found that neither cooperativity between infecting viruses, nor trans-acting factors from already infected cells, influence the timing of infection. Rather, we show experimentally that a more rapid onset of infection is explained by a first-past-the-post mechanism, where the fastest expressing virus out of the infecting virus pool sets the time for the onset of viral gene expression of an individual cell independently of other infections of the same cell. Fast onset of viral gene expression in cell-to-cell spread may play an important role in seeding the HIV reservoir, which rapidly makes infection irreversible.