Explore the vast range of titles available.

Community protective immunity can affect RNA virus evolution by selecting for new antigenic variants on the scale of years, exemplified by the need of annual evaluation of influenza vaccines. The extent to which this process termed antigenic drift affects coronaviruses remains unknown. Alike the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), seasonal human coronaviruses (HCoV) likely emerged from animal reservoirs as new human pathogens in the past. We therefore analyzed the long-term evolutionary dynamics of the ubiquitous HCoV-229E and HCoV-OC43 in comparison with human influenza A virus (IAV) subtype H3N2. We focus on viral glycoprotein genes that mediate viral entry into cells and are major targets of host neutralizing antibody responses. Maximum likelihood and Bayesian phylogenies of publicly available gene datasets representing about three decades of HCoV and IAV evolution showed that all viruses had similar ladder-like tree shapes compatible with antigenic drift, supported by different tree shape statistics. Evolutionary rates inferred in a Bayesian framework were 6.5 × 10−4 (95% highest posterior density (HPD), 5.4–7.5 × 10−4) substitutions per site per year (s/s/y) for HCoV-229E spike (S) genes and 5.7 × 10−4 (95% HPD, 5–6.5 × 10−4) s/s/y for HCoV-OC43 S genes, which were about fourfold lower than the 2.5 × 10−3 (95% HPD, 2.3–2.7 × 10−3) s/s/y rate for IAV hemagglutinin (HA) genes. Coronavirus S genes accumulated about threefold less (P < 0.001) non-synonymous mutations (dN) over time than IAV HA genes. In both IAV and HCoV, the average rate of dN within the receptor binding domains (RBD) was about fivefold higher (P < 0.0001) than in other glycoprotein gene regions. Similarly, most sites showing evidence for positive selection occurred within the RBD (HCoV-229E, 6/14 sites, P < 0.05; HCoV-OC43, 23/38 sites, P < 0.01; IAV, 13/15 sites, P = 0.08). In sum, the evolutionary dynamics of HCoV and IAV showed several similarities, yet amino acid changes potentially representing antigenic drift occurred on a lower scale in endemic HCoV compared to IAV. It seems likely that pandemic SARS-CoV-2 evolution will bear similarities with IAV evolution including accumulation of adaptive changes in the RBD, requiring vaccines to be updated regularly, whereas higher SARS-CoV-2 evolutionary stability resembling endemic HCoV can be expected in the post-pandemic stage.

Here we propose a strategy allowing implementing efficient and practicable large-scale seroepidemiological studies for Zika Virus (ZIKV). It combines screening by a commercial NS1 protein-based Zika IgG ELISA, and confirmation by a cytopathic effect-based virus neutralization test (CPE-based VNT). In post-epidemic samples from Martinique Island blood donors (a population with a dengue seroprevalence above 90%), this strategy allowed reaching specificity and sensitivity values over 98%. The CPE-based VNT consists of recording CPE directly under the optical microscope, which is easy to identify with ZIKV strain H/PF/2013 at day 5 pi. Overall, considered that CPE-based VNT is cost effective and widely automatable, the NS1 protein-based Zika IgG ELISA+CPE-based VNT combination strategy represents a convenient tool to expedite ZIKV seroprevalence studies.

Using a newly developed test for IgG antibodies based on domain III of the DENV envelope ectodomain, the authors maximise test specificity for individual serotypes, in part because they avoid cross-reactive epitopes, such as in the fusion loop of domain II. Because domains I and II are highly immunogenic, it seems likely that the underdetection of inapparent infections reported by the authors could be even more dramatic, given that flavivirus antibody test sensitivity might be reduced from not including the full ectodomain. 4 This is not a shortcoming of the study from Bos and colleagues, but simply an expected consequence of the balance between test sensitivity and specificity, which is particularly challenging for the investigation of flavivirus IgG antibodies in a setting hyperendemic for different flaviviruses, such as Zika virus (ZIKV) and DENV. 5 Their findings have important implications for attempts to estimate the number of vaccinations needed to prevent a single apparent infection; for understanding the population dynamics of DENV; and for formulating hypotheses about the potential effects of future vaccine programs to maximise cross-protection and minimise post-vaccination risks. [...]the under-reporting of dengue cases and low hospitalisation rates have major implications, particularly when evaluating vaccine efficacy based on reduced hospitalisation rates. 2 Dengue vaccines are a public health priority. Among the vaccines that have become available recently, 6–8 CYD-TDV has resulted in increased risk of developing severe dengue in vaccinated individuals not previously exposed to dengue. 9 This was at least partly due to immune enhancement, because in the case of DENV, under certain conditions, antibodies elicited during a primary infection can enhance the subsequent infection, a process termed antibody-dependent enhancement: [...]to prevent vaccine-induced enhancement of DENV infection, effective dengue vaccines must elicit a strong and highly neutralising immune response against all four DENV serotypes. 8 The disparities in disease outcomes between different dengue serotypes, especially the symptomatic and severe nature of primary DENV3 infections and frequently severe secondary DENV2 infections, globally raise some concerns about vaccine effectiveness across serotypes, mainly in seronegative individuals—all the more because the host and viral factors contributing to dengue severity are not entirely understood. 10 It is possible that studies on vaccine effectiveness and safety might need to account better for serotype-specific immunity and balanced distribution of serotypes during phase 3 trials than previously thought.

The 2023–24 Oropouche virus (OROV) outbreak in the Americas has raised public health concerns due to unprecedented numbers of confirmed cases reaching almost 10 000 reported in the WHO region of the Americas, including at least two deaths and potentially congenital infections entailing fetal death and malformations. 1 The outbreak has spanned rapidly across Bolivia, Brazil, Peru, Colombia, and Cuba, and imported cases have been detected in travellers in the USA and Europe. 2 Approximately 10 months after the onset of the Oropouche fever outbreak, substantial uncertainties remain regarding the specific factors underlying it. The pivotal study by Tiago Gräf and colleagues 6 investigates the Oropouche fever outbreak ecology and provides substantial evidence that expansion outside the Amazon biome has been more successful in small agricultural communities, particularly those cultivating bananas or cassava, where conditions likely favour proliferation of the main vector (ie, Culicoides biting midges). Serological studies can help fill these surveillance gaps by identifying lifetime exposure, but they have their own limitations, including bias from unknown travel histories of individuals and the potentially imperfect diagnostic performance of antibody tests, requiring careful validation of results using different test algorithms, which can be cumbersome to implement. 10 Thus, large-scale, multicenter, methodologically multifaceted and ideally longitudinal studies based on both presence and absence of OROV infections will be crucial to accurately capture risk factors for OROV infections, including different countries and regions and both agricultural and non-agricultural areas, and including entomovirological surveys that address vector abundance and incidence in different ecozones.

Since its discovery in 1955, the incidence and geographical spread of reported Oropouche virus (OROV) infections have increased. Oropouche fever has been suggested to be one of the most important vector-borne diseases in Latin America. However, both literature on OROV and genomic sequence availability are scarce, with few contributing laboratories worldwide. Three reassortant OROV glycoprotein gene variants termed Iquitos, Madre de Dios, and Perdões virus have been described from humans and non-human primates. OROV predominantly causes acute febrile illness, but severe neurological disease such as meningoencephalitis can occur. Due to unspecific symptoms, laboratory diagnostics are crucial. Several laboratory tests have been developed but robust commercial tests are hardly available. Although OROV is mainly transmitted by biting midges, it has also been detected in several mosquito species and a wide range of vertebrate hosts, which likely facilitates its widespread emergence. However, potential non-human vertebrate reservoirs have not been systematically studied. Robust animal models to investigate pathogenesis and immune responses are not available. Epidemiology, pathogenesis, transmission cycle, cross-protection from infections with OROV reassortants, and the natural history of infection remain unclear. This Review identifies Oropouche fever as a neglected disease and offers recommendations to address existing knowledge gaps, enable risk assessments, and ensure effective public health responses.

Since early 2024, an unprecedented spread of the Oropouche virus has been observed in Brazil and beyond in Latin America. Addressing such challenges requires a multifaceted and continent-wide approach, including improving diagnostic capabilities; enhancing surveillance, especially in settings with little economic and health resources; understanding ecological factors; and investing in treatments and possibly vaccine research. Cases Population (2022 census estimation) Incidence rate, cases per 100 000 population Human Development Index (2010) Amazonas 3231 3 941 613 81·97 0·674 Rondônia 1710 1 581 196 108·15 0·690 Bahia 888 14 141 626 6·28 0·660 Espírito Santo 479 3 833 712 12·49 0·740 Roraima 276 636 707 43·35 0·707 Acre 271 830 018 32·65 0·663 Ceará 231 8 794 957 2·63 0·682 Minas Gerais 195 20 539 989 0·95 0·731 Santa Catarina 179 7 610 361 2·35 0·774 Pernambuco 137 9 058 931 1·51 0·673 Amapá 121 733 759 16·49 0·708 Rio de Janeiro 116 16 055 174 0·72 0·761 Alagoas 115 3 127 683 3·68 0·631 Pará 93 8 121 025 1·15 0·646 Sergipe 34 2 210 004 1·54 0·665 Maranhão 33 6 755 805 0·49 0·639 Piauí 29 3 271 199 0·89 0·646 Mato Grosso 18 3 658 649 0·49 0·725 São Paulo 8 44 411 238 0·02 0·783 Tocantins 8 1 511 460 0·53 0·699 Mato Grosso do Sul 1 2 757 013 0·04 0·729 Paraíba 1 3 974 687 0·03 0·658 Distrito Federal (Federal District) 0 2 817 381 0·00 0·824 Goiás 0 7 056 495 0·00 0·735 Paraná 0 11 444 380 0·00 0·749 Rio Grande do Norte 0 3 302 729 0·00 0·684 Rio Grande do Sul 0 11 882 965 0·00 0·746 Total 8174 204 060 756 4·01 0·723 Table Oropouche virus infection cases, incidence rate, and Human Development Index score by Brazilian state

The viral family Coronaviridae comprises four genera, termed Alpha-, Beta-, Gamma-, and Deltacoronavirus. Recombination events have been described in many coronaviruses infecting humans and other animals. However, formal analysis of the recombination patterns, both in terms of the involved genome regions and the extent of genetic divergence between partners, are scarce. Common methods of recombination detection based on phylogenetic incongruences (e.g., a phylogenetic compatibility matrix) may fail in cases where too many events diminish the phylogenetic signal. Thus, an approach comparing genetic distances in distinct genome regions (pairwise distance deviation matrix) was set up. In alpha, beta, and delta-coronaviruses, a low incidence of recombination between closely related viruses was evident in all genome regions, but it was more extensive between the spike gene and other genome regions. In contrast, avian gammacoronaviruses recombined extensively and exist as a global cloud of genes with poorly corresponding genetic distances in different parts of the genome. Spike, but not other structural proteins, was most commonly exchanged between coronaviruses. Recombination patterns differed between coronavirus genera and corresponded to the modular structure of the spike: recombination traces were more pronounced between spike domains (N-terminal and C-terminal parts of S1 and S2) than within domains. The variability of possible recombination events and their uneven distribution over the genome suggest that compatibility of genes, rather than mechanistic or ecological limitations, shapes recombination patterns in coronaviruses.

A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (−29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.

Low titres might favour ADE, whereas high titres might provide cross-protection.7 Similarly, moderate titres of pre-existing antibodies against Japanese encephalitis virus were shown to prolong and increase viraemia in yellow fever vaccinees.5 Vaccination of individuals with CYD-TDV who have not been exposed to dengue virus before can increase their risk of severe disease when they are first exposed to dengue virus infection naturally.8 As a result, the WHO Strategic Advisory Group of Experts on Immunization recommended use of the vaccine only in individuals with pre-existing dengue virus immunity. In parallel, 23 million Brazilians are being vaccinated against yellow fever virus.1 The experiences from CYD-TDV trials and the magnitude of multitypic flavivirus infections in settings such as Brazil, suggest that determination of vaccine efficacy and safety in hyperendemic areas will be increasingly challenging.8 It seems likely that increasingly large numbers of individuals will have to be enrolled in vaccine trials, and long-term follow-ups will become necessary to identify severe adverse events and potential vaccination-related enhancement of subsequent flavivirus infections. [...]new tests are urgently needed to determine flavivirus serological status, ideally suitable for point-of-care testing to allow approaches that pair screening with vaccination.12 However, the complexity of flaviviral immune interplay might require determination of other flaviviruses besides dengue, and at the very least semi-quantitative techniques including innovative tools for test interpretation that are currently entirely unavailable for point-of-care testing.