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An ideal vaccine both attenuates virus growth and disease in infected individuals and reduces the spread of infections in the population, thereby generating herd immunity. Although this strategy has proved successful by generating humoral immunity to measles, yellow fever and polio, many respiratory viruses evolve to evade pre-existing antibodies1. One approach for improving the breadth of antiviral immunity against escape variants is through the generation of memory T cells in the respiratory tract, which are positioned to respond rapidly to respiratory virus infections2–6. However, it is unknown whether memory T cells alone can effectively surveil the respiratory tract to the extent that they eliminate or greatly reduce viral transmission following exposure of an individual to infection. Here we use a mouse model of natural parainfluenza virus transmission to quantify the extent to which memory CD8+ T cells resident in the respiratory tract can provide herd immunity by reducing both the susceptibility of acquiring infection and the extent of transmission, even in the absence of virus-specific antibodies. We demonstrate that protection by resident memory CD8+ T cells requires the antiviral cytokine interferon-γ (IFNγ) and leads to altered transcriptional programming of epithelial cells within the respiratory tract. These results suggest that tissue-resident CD8+ T cells in the respiratory tract can have important roles in protecting the host against viral disease and limiting viral spread throughout the population.Experiments in a mouse model of natural parainfluenza virus transmission show that tissue-resident memory T cells in the respiratory tract have important interferon-γ-dependent roles in protection against and limiting the transmission of viral disease. [ABSTRACT FROM AUTHOR]

Epidemiological models are commonly fit to case and pathogen sequence data to estimate parameters and to infer unobserved disease dynamics. Here, we present an inference approach based on sequence data that is well suited for model fitting early on during the expansion of a viral lineage. Our approach relies on a trajectory of segregating sites to infer epidemiological parameters within a Sequential Monte Carlo framework. Using simulated data, we first show that our approach accurately recovers key epidemiological quantities under a single-introduction scenario. We then apply our approach to SARS-CoV-2 sequence data from France, estimating a basic reproduction number of approximately 2.3-2.7 under an epidemiological model that allows for multiple introductions. Our approach presented here indicates that inference approaches that rely on simple population genetic summary statistics can be informative of epidemiological parameters and can be used for reconstructing infectious disease dynamics during the early expansion of a viral lineage. Epidemiological models are commonly fit to case and pathogen sequence data to estimate parameters and to reconstruct disease dynamics. Here, the authors present an inference approach based on sequence data that is well suited for model fitting early on during the expansion of a viral lineage. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) genetic exchange through reassortment has the potential to accelerate viral evolution and has played a critical role in the generation of multiple pandemic strains. For reassortment to occur, distinct viruses must co-infect the same cell. The spatio-temporal dynamics of viral dissemination within an infected host therefore define opportunity for reassortment. Here, we used wild type and synonymously barcoded variant viruses of a pandemic H1N1 strain to examine the within-host viral dynamics that govern reassortment in guinea pigs, ferrets and swine. The first two species are well-established models of human influenza, while swine are a natural host and a frequent conduit for cross-species transmission and reassortment. Our results show reassortment to be pervasive in all three hosts but less frequent in swine than in ferrets and guinea pigs. In ferrets, tissue-specific differences in the opportunity for reassortment are also evident, with more reassortants detected in the nasal tract than the lower respiratory tract. While temporal trends in viral diversity are limited, spatial patterns are clear, with heterogeneity in the viral genotypes detected at distinct anatomical sites revealing extensive compartmentalization of reassortment and replication. Our data indicate that the dynamics of viral replication in mammals allow diversification through reassortment but that the spatial compartmentalization of variants likely shapes their evolution and onward transmission. Virus reassortment drives genetic diversity and evolution and is governed by intra-host dynamics that are less well understood. Here, the authors characterise the within-host dynamics of influenza A virus reassortment in swine, ferrets and guinea pigs, considering their spatial distribution. [ABSTRACT FROM AUTHOR]

Transmission of influenza A viruses (IAV) between hosts is subject to numerous physical and biological barriers that impose genetic bottlenecks, constraining viral diversity and adaptation. The bottlenecks within hosts and their potential impacts on evolutionary pathways taken during infection are poorly understood. To address this, we created highly diverse IAV libraries bearing molecular barcodes on two gene segments, enabling high-resolution tracking and quantification of unique virus lineages within hosts. Here we show that IAV infection in lungs is characterized by multiple within-host bottlenecks that result in "islands" of infection in lung lobes, each with genetically distinct populations. We perform site-specific inoculation of barcoded IAV in the upper respiratory tract of ferrets and track viral diversity as infection spreads to the trachea and lungs. We detect extensive compartmentalization of discrete populations within lung lobes. Bottleneck events and localized replication stochastically sample individual viruses from the upper respiratory tract or the trachea that become the dominant genotype in a particular lobe. These populations are shaped strongly by founder effects, with limited evidence for positive selection. The segregated sites of replication highlight the jackpot-style events that contribute to within-host influenza virus evolution and may account for low rates of intrahost adaptation. Transmission of influenza A viruses (IAV) between hosts and replication within host impose genetic bottlenecks, constraining viral diversity and adaptation. Here, Amato et al. perform site-specific inoculation of barcoded IAV of ferrets and track viral diversity as infection spreads to the lower respiratory tract and conclude that narrow population bottlenecks are an important feature of the within-host infection dynamics. [ABSTRACT FROM AUTHOR]

How a history of influenza virus infections contributes to protection is not fully understood, but such protection might explain the contrasting age distributions of cases of the two lineages of influenza B, B/Victoria and B/Yamagata. Fitting a statistical model to those distributions using surveillance data from New Zealand, we found they could be explained by historical changes in lineage frequencies combined with cross-protection between strains of the same lineage. We found additional protection against B/Yamagata in people for whom it was their first influenza B infection, similar to the immune imprinting observed in influenza A. While the data were not informative about B/Victoria imprinting, B/Yamagata imprinting could explain the fewer B/Yamagata than B/Victoria cases in cohorts born in the 1990s and the bimodal age distribution of B/Yamagata cases. Longitudinal studies can test if these forms of protection inferred from historical data extend to more recent strains and other populations. The earliest infections with influenza A shape the immune responses to future infections, but it is not known if this phenomenon applies to influenza B. Here, the authors use influenza B case data from New Zealand and find evidence for both lineage-specific and imprinting protection. [ABSTRACT FROM AUTHOR]

Mutations can occur throughout the virus genome and may be beneficial, neutral or deleterious. We are interested in mutations that yield a C next to a G, producing CpG sites. CpG sites are rare in eukaryotic and viral genomes. For the eukaryotes, it is thought that CpG sites are rare because they are prone to mutation when methylated. In viruses, we know less about why CpG sites are rare. A previous study in HIV suggested that CpG-creating transition mutations are more costly than similar non-CpG-creating mutations. To determine if this is the case in other viruses, we analyzed the allele frequencies of CpG-creating and non-CpG-creating mutations across various strains, subtypes, and genes of viruses using existing data obtained from Genbank, HIV Databases, and Virus Pathogen Resource. Our results suggest that CpG sites are indeed costly for most viruses. By understanding the cost of CpG sites, we can obtain further insights into the evolution and adaptation of viruses. [ABSTRACT FROM AUTHOR]

An extensive body of theory addresses the topic of pathogen virulence evolution, yet few studies have empirically demonstrated the presence of fitness trade-offs that would select for intermediate virulence. Here we show the presence of transmission-clearance trade-offs in dengue virus using viremia measurements. By fitting a within-host model to these data, we further find that the interaction between dengue and the host immune response can account for the observed trade-offs. Finally, we consider dengue virulence evolution when selection acts on the virus’s production rate. By combining within-host model simulations with empirical findings on how host viral load affects human-to-mosquito transmission success, we show that the virus’s transmission potential is maximized at production rates associated with intermediate virulence and that the optimal production rate critically depends on dengue’s epidemiological context. These results indicate that long-term changes in dengue’s global distribution impact the invasion and spread of virulent dengue virus genotypes. [ABSTRACT FROM AUTHOR]

In the original article, the co-author name "Jennifer Kim" has been inadvertently missed during the publication process. The complete author group is given in this correction. [ABSTRACT FROM AUTHOR]

Outbreaks of many infectious diseases, including cholera, malaria and dengue, vary over characteristic periods longer than 1 year. Evidence that climate variability drives these interannual cycles has been highly controversial, chiefly because it is difficult to isolate the contribution of environmental forcing while taking into account nonlinear epidemiological dynamics generated by mechanisms such as host immunity. Here we show that a critical interplay of environmental forcing, specifically climate variability, and temporary immunity explains the interannual disease cycles present in a four-decade cholera time series from Matlab, Bangladesh. We reconstruct the transmission rate, the key epidemiological parameter affected by extrinsic forcing, over time for the predominant strain (El Tor) with a nonlinear population model that permits a contributing effect of intrinsic immunity. Transmission shows clear interannual variability with a strong correspondence to climate patterns at long periods (over 7 years, for monsoon rains and Brahmaputra river discharge) and at shorter periods (under 7 years, for flood extent in Bangladesh, sea surface temperatures in the Bay of Bengal and the El Niño–Southern Oscillation). The importance of the interplay between extrinsic and intrinsic factors in determining disease dynamics is illustrated during refractory periods, when population susceptibility levels are low as the result of immunity and the size of cholera outbreaks only weakly reflects climate forcing. [ABSTRACT FROM AUTHOR]

Full genome sequences are increasingly used to track the geographic spread and transmission dynamics of viral pathogens. Here, with a focus on Israel, we sequence 212 SARS-CoV-2 sequences and use them to perform a comprehensive analysis to trace the origins and spread of the virus. We find that travelers returning from the United States of America significantly contributed to viral spread in Israel, more than their proportion in incoming infected travelers. Using phylodynamic analysis, we estimate that the basic reproduction number of the virus was initially around 2.5, dropping by more than two-thirds following the implementation of social distancing measures. We further report high levels of transmission heterogeneity in SARS-CoV-2 spread, with between 2-10% of infected individuals resulting in 80% of secondary infections. Overall, our findings demonstrate the effectiveness of social distancing measures for reducing viral spread. In this study, Adi Stern and colleagues use full genome sequences of SARS-CoV-2 to look at the rate of infections in Israel. They report that social distancing had a significant effect on minimising the rate of transmission, and find evidence for transmission heterogeneity (superspreading events). [ABSTRACT FROM AUTHOR]

In this article, the authors opine on an article by Łuksza and Lässig on problems associated with addressing evolution of influenza virus and its implementation in improving seasonal-flu vaccines. They discuss mutations in epitopes of influenza virus, flu's antigenic drift, and changes in the frequencies of groups of viral strains. They also provide their views on viral strain selection for flu vaccines.

Focuses on the treatment of drug-resistant tuberculosis. Prediction of differential effects of treatment on drug-sensitive and drug-resistant strain of Mycobacterium tuberculosis.