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Western equine encephalitis virus (WEEV) is a mosquitoborne alphavirus that causes central nervous system (CNS) infection in humans and equids in the United States, Canada, and the southern cone of [...]

IntroductionLimited data exist on factors associated with concurrent use patterns of electronic nicotine delivery systems (ENDS) and cigarettes. We examined longitudinally perceptions and experiences with ENDS in relationship to concurrent use patterns among established, recent smokers who recently initiated ENDS.MethodsParticipant recruitment took place using paid digital advertisements on social media. Between December 2020 and October 2021, 303 adults aged ≥21 years from across the US who currently or recently smoked and had initiated ENDS use within the past 30 days or reinitiated ENDS use after more than one year of non-use were surveyed. Multinomial logistic regressions were conducted to analyze association between the outcome of current use pattern at follow-up at 1 month [rejectors (discontinued ENDS, continued smoking), primary smokers (concurrent users, mostly smoke), dual user (similar smoking and ENDS use), primary vapers (concurrent users, mostly vape), and switchers (discontinued smoking, continued using ENDS) or quitters (discontinued both smoking and ENDS] and perceptions of and experiences with ENDS predictors at baseline.ResultsAt follow-up at 1 to 2 months after initiating ENDS, 20% were rejectors, 31% were primary smokers, 13% were dual users, 19% were primary vapers, and 17% were switchers/quitters. Perceiving ENDS as less harmful than smoking or being uncertain and as equally or more enjoyable smoking, experiencing a lot or complete reduction in cravings to smoking and in irritability with ENDS use, liking the taste of ENDS, and being satisfied with vaping were associated with higher odds of quitting smoking compared to rejecting ENDS or mostly smoking at follow-up at 1 month.ConclusionsFindings highlight the importance of initial ENDS perceptions and experiences when examining tobacco outcomes and potentially for developing policies and interventions targeting smoking cessation. ENDS initiators are differentiating into distinct use patterns based on these factors within a short period of time.

Mayaro virus (MAYV) is an endemic and neglected mosquitoborne alphavirus that causes acute and chronic debilitating arthritogenic disease in Latin America and the Caribbean (1). MAYV infection can cause fever, [...]

Kedougou, Senegal's southeastern region, is a substantial arbovirus hotspot (1,2). Decades of comprehensive surveillance have existed through both a nationwide Syndromic Sentinel Surveillance Network (3) and passive surveillance in several [...]

Chikungunya virus (CHIKV) is a mosquitoborne alphavirus that has caused >10 million cases in >125 countries and territories in the past 2 decades. Chikungunya disease is characterized by acute and [...]

Understanding the molecular basis of innate immune evasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important consideration for designing the next wave of therapeutics. Here, we investigate the role of the nonstructural protein 16 (NSP16) of SARS-CoV-2 in infection and pathogenesis. NSP16, a ribonucleoside 2'-O-methyltransferase (MTase), catalyzes the transfer of a methyl group to mRNA as part of the capping process. Based on observations with other CoVs, we hypothesized that NSP16 2'-O-MTase function protects SARS-CoV-2 from cap-sensing host restriction. Therefore, we engineered SARS-CoV-2 with a mutation that disrupts a conserved residue in the active site of NSP16. We subsequently show that this mutant is attenuated both in vitro and in vivo, using a hamster model of SARS-CoV-2 infection. Mechanistically, we confirm that the NSP16 mutant is more sensitive than wild-type SARS-CoV-2 to type I interferon (IFN-I) in vitro. Furthermore, silencing IFIT1 or IFIT3, IFN-stimulated genes that sense a lack of 2'-O-methylation, partially restores fitness to the NSP16 mutant. Finally, we demonstrate that sinefungin, an MTase inhibitor that binds the catalytic site of NSP16, sensitizes wild-type SARS-CoV-2 to IFN-I treatment and attenuates viral replication. Overall, our findings highlight the importance of SARS-CoV-2 NSP16 in evading host innate immunity and suggest a target for future antiviral therapies. IMPORTANCE Similar to other coronaviruses, disruption of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) NSP16 function attenuates viral replication in a type I interferon-dependent manner. In vivo, our results show reduced disease and viral replication at late times in the hamster lung, but an earlier titer deficit for the NSP16 mutant (dNSP16) in the upper airway. In addition, our results confirm a role for IFIT1 but also demonstrate the necessity of IFIT3 in mediating dNSP16 attenuation. Finally, we show that targeting NSP16 activity with a 2'-O-methyltransferase inhibitor in combination with type I interferon offers a novel avenue for antiviral development.

The objective of this study was to determine the etiology of febrile illnesses among patients from October 1, 1993 through September 30, 1999, in the urban community of Iquitos in the Amazon River Basin of Peru. Epidemiological and clinical data as well as blood samples were obtained from consenting patients at hospitals, health clinics and private residences. Samples were tested for arboviruses in cell cultures and for IgM and IgG antibodies by ELISA. Blood smears were examined for malaria, and sera were tested for antibodies to Leptospira spp. by ELISA and microscopic agglutination. Among 6,607 febrile patients studied, dengue viruses caused 14.6% of the cases, and Venezuelan equine encephalitis virus caused 2.5%, Oropouche virus 1.0%, Mayaro virus 0.4%, and other arboviruses caused 0.2% of the cases. Also, 22.9% of 4,844 patients tested were positive for malaria, and of 400 samples tested, 9% had evidence of acute leptospirosis. Although the study was not designed to assess the importance of these pathogens as a cause of human morbidity in the total population, these results indicate that arboviruses, leptospirosis, and malaria were the cause of approximately 50% of the febrile cases. Although the arboviruses that were diagnosed can produce asymptomatic infections, our findings increased the overall understanding of the relative health burden of these infections, as well as baseline knowledge needed for designing and implementing further studies to better assess the health impact and threat of these pathogens in the Amazon Basin of Peru.

Chikungunya (CHIKV) is an emerging worldwide viral threat. The immune response to infection can lead to protection and convalescence or result in long-term sequelae such as arthritis. Early innate immune events during acute infection have been characterized for some cell types, but more must be elucidated with respect to cellular responses of monocytes and other myeloid lineage cells. In addition to their roles in protection and inflammation resolution, monocytes and macrophages are sites for viral replication and may also act as viral reservoirs. These cells are also found in joints postinfection, possibly playing a role in long-term CHIKV-induced pathology. We examined kinetic and phenotypic changes in myeloid lineage cells, including monocytes, in cynomolgus macaques early after experimental infection with CHIKV. We found increased proliferation of monocytes and decreased proliferation of myeloid dendritic cells early during infection, with an accompanying decrease in absolute numbers of both cell types, as well as a simultaneous increase in plasmacytoid dendritic cell number. An increase in CD16 and CD14 was seen along with a decrease in monocyte Human Leukocyte Antigen-DR isotype expression within 3 days of infection, potentially indicating monocyte deactivation. A transient decrease in T cells, B cells, and natural killer cells correlated with lymphocytopenia observed during human infections with CHIKV. CD4+ T cell proliferation decreased in blood, indicating relocation of cells to effector sites. These data indicate CHIKV influences proliferation rates and kinetics of myeloid lineage cells early during infection and may prove useful in development of therapeutics and evaluation of infection-induced pathogenesis.

There is an increasing global burden from chikungunya virus (CHIKV). Bangladesh reported a major epidemic in 2017, but it was unclear whether there had been prior widespread transmission. We conducted a nationally representative seroprevalence survey in 70 randomly selected communities immediately before the epidemic. We found that 69 of 2938 sampled individuals (2.4%) were seropositive to CHIKV. Seropositivity to dengue virus (adjusted odds ratio, 3.13 [95% confidence interval, 1.86–5.27]), male sex (0.59 [.36–.99]), and community presence of Aedes aegypti mosquitoes (1.80 [1.05–3.0]7) were significantly associated with CHIKV seropositivity. Using a spatial prediction model, we estimated that across the country, 4.99 (95% confidence interval, 4.89–5.08) million people had been previously infected. These findings highlight high population susceptibility before the major outbreak and that previous outbreaks must have been spatially isolated. [ABSTRACT FROM AUTHOR]

During the recent yellow fever (YF) epidemics in Brazil, human cases were attributed to spillover infections via sylvatic mosquito transmission. Despite YF virus (YFV) transmission in major urban centers with insufficient vaccination coverage and abundant populations of the domestic vector, Aedes aegypti, there was no evidence of human-amplified transmission. Furthermore, the historic absence of YF in Asia, despite abundant Ae. aegypti and an immunologically naive human population, is unexplained. We tested the hypothesis that pre-existing, heterologous flavivirus immunity, specifically from dengue (DENV) and Zika (ZIKV) viruses, limits YFV viremia and transmission by Ae. aegypti. We infected cynomolgus macaques with DENV or ZIKV, then challenged them 6–9 months later with YFV. We then measured viremia and disease and allowed Ae. aegypti mosquitoes to feed during peak macaque viremia. Although prior heterologous immunity had variable effects on disease, DENV and ZIKV immunity consistently suppressed YFV viremia. Despite no statistical difference due to a small sample size, the suppression in viremia led to a significant reduction in Ae. aegypti infection and a lack of transmission potential. These results support the hypothesis that, in DENV- and ZIKV-endemic regions such as South America and Asia, human flavivirus immunity suppresses YFV human amplification potential, reducing the risk of urban outbreaks. Epidemiology of yellow fever suggests that other flaviviruses may provide some level of cross-protection. Here the authors show in a non-human primate model that pre-existing dengue-2 or Zika virus immunity results in lower yellow fever viremia compared to naïve animals, limiting the transmission potential by Aedes aegypti mosquitoes. [ABSTRACT FROM AUTHOR]

While first-generation, spike (S)-based COVID-19 vaccines were effective against early SARS-CoV-2 strains, the rapid evolution of novel Omicron subvariants have substantially reduced vaccine efficacy. As such, broadly protective vaccines against SARS-CoV-2 are needed to prevent future viral emergence. In addition, it remains less clear whether peripheral immunization, especially with mRNA vaccines, elicits effective respiratory immunity. Our group has developed a nucleoside-modified mRNA vaccine expressing the nucleocapsid (N) protein of the ancestral SARS-CoV-2 virus and has tested its use in combination with the S-based mRNA vaccine (mRNA-S). In this study, we examined efficacy of mRNA-N alone or in combination with mRNA-S (mRNA-S+N) against more immune evasive Omicron variants in hamsters. Our data show that mRNA-N alone induces a modest but significant protection against BA.5 and that dual mRNA-S+N vaccination confers complete protection against both BA.5 and BQ.1, preventing detection of virus in the hamster lungs. Analysis of respiratory immune response in mice shows that intramuscular mRNA-S+N immunization effectively induces respiratory S- and N-specific T cell responses in the lungs and in bronchoalveolar lavage (BAL), as well as antigen-specific binding IgG in BAL. Together, our data further support mRNA-S+N as a potential pan-COVID-19 vaccine for broad protection against current and emerging SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]