The convergence strategies of antigenic subunits and synthetic nanoparticle scaffold platform improve the vaccine production efficiency and enhance vaccine-induced immunogenicity. Selecting the appropriate nanoparticle scaffold is crucial to controlling target antigens immunologically. Lumazine synthase (LS) is an attractive candidate for a vaccine display system due to its thermostability, modification tolerance, and morphological plasticity. Here, the first development of a multivalent thermostable scaffold, LS-SUMO (SUMO, small ubiquitin-likemodifier), and a divalent nanovaccine covalently conjugated with Chikungunya virus E2 and Zika virus EDIII antigens, is reported. Compared with antigen monomers, LS-SUMO nanoparticle vaccines elicit a higher humoral response and neutralizing antibodies against both antigen targets in mouse sera. Mice immunized with LS-SUMO conjugates produce CD4+ T cell-mediated Th2-biased responses and promote humoral immunity. Importantly, LS-SUMO conjugates possess equivalent humoral immunogenicity after heat treatment. Taken together, LS-SUMO is a powerful biotargeting nanoplatform with high-yield production, thermal stability and opens a new avenue for multivalent presentation of various antigens.

Aedes-borne arboviral diseases were important public health problems in Zhejiang before the coronavirus disease 2019 (COVID-19) pandemic. This study was conducted to investigate the characteristics and change of the epidemiology of Aedes-borne arboviral diseases in the province.
Descriptive analyses were conducted to summarize the epidemiology of Aedes-borne arboviral diseases during 2003-2022.
A total of 3,125 cases, including 1,968 indigenous cases, were reported during 2003-2022. Approximately three-quarters of imported cases were infected from Southeast Asia. The number of annual imported cases increased during 2013-2019 (R2 = 0.801, p = 0.004) and peaked in 2019. When compared with 2003-2012, all prefecture-level cities witnessed an increase in the annual mean incidence of imported cases in 2013-2019 (0.11-0.42 per 100,000 population vs. 0-0.05 per 100,000 population) but a drastic decrease during 2020-2022 (0-0.03 per 100,000 population). The change in geographical distribution was similar, with 33/91 counties during 2003-2012, 86/91 during 2013-2019, and 14/91 during 2020-2022. The annual mean incidence of indigenous cases in 2013-2019 was 7.79 times that in 2003-2012 (0.44 vs. 0.06 per 100,000 population). No indigenous cases were reported between 2020-2022. Geographical extension of indigenous cases was also noted before 2020-from two counties during 2003-2012 to 44 during 2013-2019.
Dengue, chikungunya fever, zika disease, and yellow fever are not endemic in Zhejiang but will be important public health problems for the province in the post-COVID-19 era.

The co-circulation of different emerging viral diseases is a big challenge from an epidemiological point of view. The similarity of symptoms, cases of virus co-infection, and cross-reaction can mislead in the diagnosis of the disease. In this article, a new mathematical model for COVID-19, zika, chikungunya, and dengue co-dynamics is developed and studied to assess the impact of COVID-19 on zika, dengue, and chikungunya dynamics and vice-versa. The local and global stability analyses are carried out. The model is shown to undergo a backward bifurcation under a certain condition. Global sensitivity analysis is also performed on the parameters of the model to determine the most dominant parameters. If the zika-related reproduction number ℛ 0Z is used as the response function, then important parameters are: the effective contact rate for vector-to-human transmission of zika ( β 2 h , which is positively correlated), the human natural death rate ( ϑ h , positively correlated), and the vector recruitment rate ( Ψ v , also positively correlated). In addition, using the class of individuals co-infected with COVID-19 and zika ( ℐ CZ h ) as response function, the most dominant parameters are: the effective contact rate for COVID-19 transmission ( β 1 , positively correlated), the effective contact rate for vector-to-human transmission of zika ( β 2 h , positively correlated). To control the co-circulation of all the diseases adequately under an endemic setting, time dependent controls in the form of COVID-19, zika, dengue, and chikungunya preventions are incorporated into the model and analyzed using the Pontryagin\'s principle. The model is fitted to real COVID-19, zika, dengue, and chikungunya datasets for Espirito Santo (a city with the co-circulation of all the diseases), in Brazil and projections made for the cumulative cases of each of the diseases. Through simulations, it is shown that COVID-19 prevention could greatly reduce the burden of co-infections with zika, dengue, and chikungunya. The negative impact of the COVID-19 pandemic on the control of the arbovirus diseases is also highlighted. Furthermore, it is observed that prevention controls for zika, dengue, and chikungunya can significantly reduce the burden of co-infections with COVID-19.

Skeletal muscle development plays a vital role in muscle quality and yield in meat rabbits. Circular RNAs (circRNAs) are a new type of single-stranded endogenous non-coding RNAs involved in different biological processes. However, our knowledge of circRNAs regulating skeletal muscle development remains largely unknown in meat rabbits. In this study, we collected the leg muscle tissues of ZIKA rabbits at three key growth stages. By performing whole-transcriptome sequencing, we found the sequential expression of day 0- (D0-), D35-, and D70-selective mRNAs mainly functioned in muscle development, nervous development, and immune response during skeletal muscle development, respectively. Then, a combination of circRNA assembly from a circRNA-seq library and the whole-transcriptome sequencing data identified 6845 credible circRNAs in our samples. Most circRNAs were transcribed from exons of known genes, contained few exons, and showed short length, and these circRNAs were more conserved between rabbits and humans than between rabbits and mice. The upregulated circRNAs, which were synchronously changed with host genes, primarily played roles in MAPK signaling pathways and fatty acid biosynthesis. The prediction of circRNA-microRNA-mRNAs networks revealed that circRNAs might be the regulators that mainly functioned in rabbits\' muscle neuron development and metabolic processes. Our work provides a catalog of circRNAs regulating skeletal muscle development at key growth stages in rabbits and might give a new insight into rabbit breeding.

In co-infection models for two diseases, it is mostly claimed that, the dynamical behavior of the sub-models usually predict or drive the behavior of the complete models. However, under a certain assumption such as, allowing incident co-infection with both diseases, we have a different observation. In this paper, a new mathematical model for SARS-CoV-2 and Zika co-dynamics is presented which incorporates incident co-infection by susceptible individuals. It is worth mentioning that the assumption is missing in many existing co-infection models. We shall discuss the impact of this assumption on the dynamics of a co-infection model. The model also captures sexual transmission of Zika virus. The positivity and boundedness of solution of the proposed model are studied, in addition to the local asymptotic stability analysis. The model is shown to exhibit backward bifurcation caused by the disease-induced death rates and parameters associated with susceptibility to a second infection by those singly infected. Using Lyapunov functions, the disease free and endemic equilibria are shown to be globally asymptotically stable for R 0 1 , respectively. To manage the co-circulation of both infections effectively, under an endemic setting, time dependent controls in the form of SARS-CoV-2, Zika and co-infection prevention strategies are incorporated into the model. The simulations show that SARS-CoV-2 prevention could greatly reduce the burden of co-infections with Zika. Furthermore, it is also shown that prevention controls for Zika can significantly decrease the burden of co-infections with SARS-CoV-2.

OBJECTIVE: This study intended to compare the effectiveness of thematic maps with that of tabular data in comprehension and memory of risk magnitudes, with Zika virus (ZIKV) disease outbreaks in the United States as the subject matter. The study also aimed to examine the effects of data presentation format and past occurrence information on risk perception and risk avoidance intention.
METHODS: This study used an experiment.
METHODS: Each participant was randomly assigned to view ZIKV disease 2017 incidence data presented in one of the three formats: a choropleth map, a graduated-circle map, and a table, after which they answered questions about comprehension and memory of risk magnitudes. Each participant was then randomly assigned to view or not to view incidence data of the previous occurrence of ZIKV outbreaks in 2016, after which they answered questions about risk perception and risk avoidance intention.
RESULTS: The results revealed the effectiveness of thematic maps over tabular data in comprehension, risk perception, and risk avoidance intention. Compared to tabular data, the choropleth map led to a better comprehension of relative risk magnitudes, the graduated-circle map led to higher risk perception, and both thematic maps led to greater risk avoidance intention. In contrast, tabular data led to better recognition of absolute risk magnitudes than both thematic maps. In addition, past occurrence information enhanced risk perception and risk avoidance intention.
CONCLUSIONS: The findings reveal the importance of data presentation format in comprehension and memory of risk magnitudes. This can be attributed to the cognitive match between the information emphasized in the presentation and that required by the tasks. The findings also suggest that data presentation format and past occurrence information are important judgmental heuristics that help to form risk perception and risk avoidance intention.

Sexual transmission of Zika Virus (ZIKV) elevates the risk of its dissemination in the female reproductive tract and causes a serious threat to the fetus. However, the available animal models are not appropriate to investigate sexual transmission, dynamics of ZIKV infection, replication, and shedding. The use of tree shrew as a small animal model of ZIKV vaginal infection was assessed in this study. A total of 23 sexually mature female tree shrews were infected with ZIKV GZ01 via the intravaginal route. There was no significant difference in change of body weight, and the temperature between ZIKV infected and control animals. Viral RNA loads were detected in blood, saliva, urine, and vaginal douching. ZIKV RNA was readily detected in vaginal lavage of 22 animals (95.65%, 22/23) at 1 dpi, and viral load ranged from 104.46 to 107.35 copies/ml, and the peak of viral load appeared at 1 dpi. The expression of key inflammatory genes, such as IL6, 8, CCL5, TNF-a, and CXCL9, was increased in the spleen of ZIKV infected animals. In the current study, female tree shrews have been successfully infected with ZIKV through the vaginal route for the first time. Interestingly, at first, ZIKV replicates at the local site of infection and then spreads throughout the host body to develop a robust systemic infection and mounted a protective immune response. This small animal model is not only valuable for exploring ZIKV sexual transmission and may also help to explain the cause of debilitating manifestations of the fetus in vivo.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that poses significant threats to global public health. Macrophages and dendritic cells are both key sentinel cells in the host immune response and play critical roles in the pathogenesis of flavivirus infections. Recent studies showed that ZIKV could productively infect monocyte-derived dendritic cells (moDCs), but the role of macrophages in ZIKV infection remains incompletely understood. In this study, we first compared ZIKV infection in monocyte-derived macrophages (MDMs) and moDCs derived from the same donors. We demonstrated that while both MDMs and moDCs were susceptible to epidemic (Puerto Rico) and pre-epidemic (Uganda) strains of ZIKV, virus replication was largely restricted in MDMs but not in moDCs. ZIKV induced significant apoptosis in moDCs but not MDMs. The restricted virus replication in MDMs was not due to inefficient virus entry but was related to post-entry events in the viral replication cycle. In stark contrast with moDCs, ZIKV failed to inhibit STAT1 and STAT2 phosphorylation in MDMs. This resulted in the lack of efficient antagonism of the host type I interferon-mediated antiviral responses. Importantly, depletion of STAT2 but not STAT1 in MDMs significantly rescued the replication of ZIKV and the prototype flavivirus yellow fever virus. Overall, our findings revealed a differential interplay between macrophages and dendritic cells with ZIKV. While dendritic cells may be exploited by ZIKV to facilitate virus replication, macrophages restricted ZIKV infection.

Japanese encephalitis virus (JEV) exposure or vaccination could elicit cross-reactive CD8 T cell immunity against heterologous flaviviruses in humans. In addition, cross-reactive CD8 T cells induced by dengue virus (DENV) have been shown to play a protective role against Zika virus (ZIKV). However, how JEV exposure or vaccination affects ZIKV infection in humans remains unclear. In this report, epitope prediction algorithms were used to predict the cross-reactive CD8 T cell epitope restricted to human HLA between JEV and ZIKV. We found that these predicted CD8 T cell epitopes are immunogenic and cross-reactive in humanized HLA transgenic mice. Moreover, JEV vaccine immunization provided cross-protection against ZIKV infection. Furthermore, CD8 T cells were involved in the protection against ZKIV infection in vivo. Our results have an important clinical implication that vaccination with JEV SA14-14-2 may provide protection against ZIKV infection in humans.

As traditional approaches to the control of dengue and Zika are insufficient, significant efforts have been made to develop utilization of the endosymbiotic bacterium Wolbachia to reduce the ability of mosquitoes to transmit pathogens. Although Wolbachia is known to inhibit flaviviruses in mosquitoes, including dengue virus (DENV) and Zika virus (ZIKV), it remains unclear how the endosymbiont interferes with viral replication cycle. In this study, we have carried out viral binding assays to investigate the impact of the Wolbachia strain wAlbB on the attachment of DENV serotype 2 (DENV-2) and ZIKV to Aedes aegypti Aag-2 cells. RNA interference (RNAi) was used to silence a variety of putative mosquito receptors of DENV that were differentially regulated by wAlbB in Aag-2 cells, in order to identify host factors involved in the inhibition of viral binding. Our results showed that, in addition to suppression of viral replication, Wolbachia strongly inhibited binding of both DENV-2 and ZIKV to Aag-2 cells. Moreover, the expression of two putative mosquito DENV receptors - dystroglycan and tubulin - was downregulated by wAlbB, and their knock-down resulted in the inhibition of DENV-2 binding to Aag-2 cells. These results will aid in understanding the Wolbachia-DENV interactions in mosquito and the development of novel control strategies for mosquito-borne diseases.