Group A rotavirus remains a major pathogen causing infantile diarrhea. Although rotaviruses are known for their zoonotic potential and frequent genomic reassortment, the virological features of newly isolated strains and their suitability as vaccine candidates remain unclear. In this study, a human rotavirus strain of genotype G3P[10] was isolated from the fecal sample of an infant with diarrhea in Xiangyun County, Yunnan Province, China in 2019, and subsequently cultured in MA104 cells in 2021. The strain was designated XYR-19. Its biological characteristics were assessed through morphological examination, serological testing, and molecular analyses. Whole-genome sequencing and bioinformatic approaches were then used to define its genetic profile. Similarly, an inactivated vaccine was prepared based on this strain and evaluated its immunogenicity. Biological characterization confirmed that XYR-19 demonstrated stable structural and replication properties, reaching a viral titer of 7.3 lg CCID₅₀/mL after propagation. Whole-genome sequencing revealed a genotype constellation of G3-P[10]-I8-R3-C3-M3-A9-N3-T3-E3-H6. Comparative analysis indicated that the VP4 and VP7 genes shared 99.41% and 96.57% nucleotide identity, respectively, with the circulating domestic strain bat-derived strain MYAS33, while also harboring distinct mutation sites. Phylogenetic analysis showed that XYR-19 clustered closely with human RVA strain MS2015-1-0001, CMH079, and CMH-S015-19. These findings expand current knowledge of rotavirus epidemiology in the region and provide essential data for tracking local transmission dynamics. Moreover, they offer a valuable basis for future rotavirus vaccine development and for designing strategies aimed at limiting cross-species transmission, ultimately supporting improved prevention and control of infantile diarrhea in the area.

Inactivated rotavirus vaccines (IRV) are an effective approach for providing protection against the virus. This double-blind, randomised, placebo-controlled, dose-escalation phase I trial evaluated the safety and immunogenicity of IRV in 288 healthy children aged 2–71 months without prior rotavirus vaccination or HIV infection. We stratified participants by age (7–71 months and 2–6 months) and schedule (2 or 3 doses), before randomising them 3:1 to receive one of three antigen doses (80, 160, or 320 ELISA Unit [EU]), or aluminium adjuvanted placebo. The primary endpoints included adverse reactions/events within 30 min post-dose, adverse reactions/events during days 0–7 and 8–28/30 post-dose, and serious adverse events (SAEs) 6 months after the full course. The secondary endpoints were neutralizing antibody (NTA) geometric mean titres (GMT) and seroconversion rates (≥4-fold rise) at day 28 post-final dose. IRV was well tolerated, with no vaccine-related SAEs in any of the cohorts; we observed clinically manageable transient mild-to-moderate fever in the high dose infant group. Dose-dependent increases in NTA and IgG antibody responses were observed across all cohorts. In the 3-dose infant group, the 320 EU dose yielded a GMT of 551.98 (95% CI 338.39 ~ 900.40) compared to 36.17 for placebo, and a seroconversion rate of 83.33% (vs. 10.00% for placebo); the 3-dose schedule outperformed the 2-dose regimen. Our findings confirm that IRV has a favourable safety and immunogenicity profile. This trial is registered with ClinicalTrials.gov (NCT04626856). This double-blind, randomized, placebo-controlled, dose escalation phase I trial evaluates the safety and immunogenicity of an inactivated rotavirus vaccine (IRV) in healthy young children and infants without prior rotavirus vaccination or HIV infection.

Rotavirus (RV) is the primary cause of severe gastroenteritis in young children, yet the long noncoding RNA (lncRNA) regulatory landscape governing the host response remains largely unmapped. To address this gap, the present study performed an integrated transcriptomic analysis of mRNA and lncRNA expression profiles in RV-infected MA104 cells at 24 h post-infection. Deep sequencing identified 11,919 high-confidence lncRNAs, revealing a massive transcriptional shift: 3651 mRNAs and 4655 lncRNAs were differentially expressed, with both populations predominantly upregulated. Functional enrichment analysis confirmed the strong activation of key innate immunity pathways, including the RIG-I-like receptor, Toll-like receptor, and TNF signaling pathways. Conversely, fundamental metabolic pathways were found to be suppressed. Crucially, the analysis of lncRNA targets highlighted their involvement in coordinating the host antiviral defense, particularly through transregulation. Experimental validation confirmed the significant upregulation of key immune-related mRNAs (OASL and C3) as well as two novel lncRNAs (lncRNA-6479 and lncRNA-4290) by qRT-PCR. The significant upregulation of OASL and C3 was validated at the protein level, confirming the biological relevance of the transcriptomic data. This study provides a foundational, genome-wide resource, identifying novel lncRNA targets for future mechanistic investigation into host-RV interactions.

Antiviral effectors and cytokines are critical components of host innate immunity. However, the regulatory mechanisms governing the roles of these molecules in host-virus interactions are still unclear. Although long non-coding RNAs (lncRNAs) have been recognized as key players in various biological processes, their involvement in the complement system of host antiviral defenses remains to be explored. In this study, we discovered a novel, unannotated lncRNA, called DARVR. DARVR was found to be an intergenic lncRNA and inhibited rotavirus (RV) replication in MA104 cells. Mechanistically, we found that complement 3 (C3) was upregulated following RV infection in a LAMB1-dependent manner. However, LAMB1 expression was downregulated by miR-365-1-5p, resulting in the inhibition of the C3-mediated antiviral reaction. However, DARVR functioned as a competing endogenous RNA against miR-365-1-5p, promoting the expression of LAMB1 and thereby enhancing C3 activity and inhibiting RV replication. These results not only provide evidence demonstrating the involvement of lncRNAs in the regulation of RV infection but also highlight the role of complement factors in host innate immunity. IMPORTANCE:Long non-coding RNAs (lncRNAs) play versatile and critical roles in host-virus interactions, offering significant potential for developing targeted therapies to prevent or treat viral infections. Despite their importance, the involvement of lncRNAs in rotavirus infection remains underexplored. This study identifies a novel lncRNA that enhances complement factor C3 activity through the competing endogenous RNA (ceRNA) mechanism, effectively inhibiting rotavirus replication across different subtypes. These findings underscore the complex molecular interplay regulating complement factor activity during rotavirus infection and provide valuable insights into the host's antiviral mechanisms. This research paves the way for innovative therapeutic strategies targeting lncRNAs and complement factors to combat viral infections more effectively.

Background: We performed a phase I experiment in a healthy teenage population in Sui County, Henan Province, China. The trial was randomized, double-blind, and placebo-controlled. Methods: Ninety-six adolescents were randomly assigned in three groups (high-dose, medium-dose, and low-dose) to receive a dose of the vaccine or the placebo. The patients were monitored for adverse events (AEs) for up to 30 days after each dose of the vaccine and for up to 6 months after all doses of serious AEs (SAEs). All observed AEs and SAEs were reported. Microneutralization assays were used to measure geometric mean titers (GMTs) and seroconversion rates for neutralizing antibodies. IgA and IgG antibodies specific to the rotavirus were detected. Results: The rates of total AEs in these groups were 8.33%, 37.50%, 12.50%, and 4.17%, respectively. The neutralizing antibody test revealed that the teenage groups with low, medium, and high doses of the vaccine had geometric mean titers of 424.32, 504.63, and 925.45, respectively, at 28 days following complete vaccination. The GMT of serum IgG at final immunization was 6501.86, 6501.82, and 10,173.3, in the low-dose, medium-dose, and high-dose groups, respectively. The GMT of serum IgA at final immunization was 2733.64, 2233.29, and 3596.66 in the low-dose, medium-dose group, and high-dose groups, respectively. Conclusions: The majority of adverse events (AEs) were deemed Grade 1 or 2, suggesting that the vaccine’s safety profile is suitable for healthy adolescents. For the primary immunogenicity endpoints, a preliminary examination of the GMTs and the positive transfer rate of neutralizing antibodies in the different experimental groups revealed that, in adolescents aged 6–17, the high-dose group displayed significantly higher levels of neutralizing antibodies compared to the medium- and low-dose groups. Adolescents had few side effects from the new inactivated rotavirus vaccination, and it elicited an immune response.

Rotavirus is a major cause of severe diarrhea and mortality in children under five years of age, leading to approximately 128,500 deaths annually.1-3 Vaccination is the most effective strategy for preventing rotavirus infection. While two widely used vaccines, Rotarix and RotaTeq, have shown good efficacy in high-income countries, their effectiveness is lower in low- and middle-income countries due to factors such as malnutrition and poor sanitation.4-6 These challenges include complex vaccination schedules and high production costs. Researchers are working on novel vaccines, including inactivated virus and viral protein-based options, as well as virus-like particles and recombinant proteins.7-9 Improving vaccine stability and applicability is crucial for resource-limited settings, and global vaccination strategies are expected to significantly reduce infection burdens, improve child health, and contribute to the achievement of global health goals.10-14.

Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus drugs are available. It is crucial to develop effective and low-toxicity anti-rotavirus small-molecule drugs that act on novel host targets. In this study, a new anti-rotavirus compound was selected by ELISA, and cell activity was detected from 453 small-molecule compounds. The anti-RV effects and underlying mechanisms of the screened compounds were explored. In vitro experimental results showed that the small-molecule compound ML241 has a good effect on inhibiting rotavirus proliferation and has low cytotoxicity during the virus adsorption, cell entry, and replication stages. In addition to its in vitro effects, ML241 also exerted anti-RV effects in a suckling mouse model. Transcriptome sequencing was performed after adding ML241 to cells infected with RV. The results showed that ML241 inhibited the phosphorylation of ERK1/2 in the MAPK signaling pathway, thereby inhibiting IκBα, activating the NF-κB signaling pathway, and playing an anti-RV role. These results provide an experimental basis for specific anti-RV small-molecule compounds or compound combinations, which is beneficial for the development of anti-RV drugs.

We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly assigned to one of three groups (high-dose, medium-dose, and low-dose) at a 3:1 ratio to receive one vaccine dose or placebo. Adverse events up to 28 days after each dose and serious adverse events up to 6 months after all doses were reported. Geometric mean titers and seroconversion rates were measured for anti-rotavirus neutralizing antibodies using microneutralization tests. The rates of total adverse events in the placebo group, low-dose group, medium-dose group, and high-dose group were 29.17 % (12.62 %-51.09 %), 12.50 % (2.66 %-32.36 %), 50.00 % (29.12 %-70.88 %), and 41.67 % (22.11 %-63.36 %), respectively, with no significant difference in the experimental groups compared with the placebo group. The results of the neutralizing antibody assay showed that in the adult group, the neutralizing antibody geometric mean titer at 28 days after full immunization in the low-dose group was 583.01 (95 % confidence interval [CI]: 447.12-760.20), that in the medium-dose group was 899.34 (95 % CI: 601.73-1344.14), and that in the high-dose group was 1055.24 (95 % CI: 876.28-1270.75). The GMT of serumspecific IgG at 28 days after full immunization in the low-dose group was 3444.26 (95 % CI: 2292.35-5175.02), that in the medium-dose group was 6888.55 (95 % CI: 4426.67-10719.6), and that in the high-dose group was 7511.99 (95 % CI: 3988.27-14149.0). The GMT of serum-specific IgA at 28 days after full immunization in the low-dose group was 2332.14 (95 % CI: 1538.82-3534.45), that in the medium-dose group was 4800.98 (95 % CI: 2986.64-7717.50), and that in the high-dose group was 3204.30 (95 % CI: 2175.66-4719.27). In terms of safety, adverse events were mainly Grades 1 and 2, indicating that the safety of the vaccine is within the acceptable range in the healthy adult population. Considering the GMT and positive transfer rate of neutralizing antibodies for the main immunogenicity endpoints in the experimental groups, it was initially observed that the high-dose group had higher levels of neutralizing antibodies than the medium- and low-dose groups in adults aged 18-49

Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of live attenuated RV vaccines or developing non-replicating RV (e.g., mRNA) vaccines is crucial for reducing the morbidity and mortality from RV infections. Herein, a nucleoside-modified mRNA vaccine encapsulated in lipid nanoparticles (LNP) and encoding the VP7 protein from the G1 type of RV was developed. The 5′ untranslated region of an isolated human RV was utilized for the mRNA vaccine. After undergoing quality inspection, the VP7-mRNA vaccine was injected by subcutaneous or intramuscular routes into mice. Mice received three injections in 21 d intervals. IgG antibodies, neutralizing antibodies, cellular immunity, and gene expression from peripheral blood mononuclear cells were evaluated. Significant differences in levels of IgG antibodies were not observed in groups with adjuvant but were observed in groups without adjuvant. The vaccine without adjuvant induced the highest antibody titers after intramuscular injection. The vaccine elicited a potent antiviral immune response characterized by antiviral clusters of differentiation CD8+ T cells. VP7-mRNA induced interferon-γ secretion to mediate cellular immune responses. Chemokine-mediated signaling pathways and immune response were activated by VP7-mRNA vaccine injection. The mRNA LNP vaccine will require testing for protective efficacy, and it is an option for preventing rotavirus infection.

Rotavirus is one of the main pathogens causing severe diarrhea in infants and young children < 5 years of age. The development of the next-generation rotavirus vaccine is of great significance for preventing rotavirus infection and reducing severe mortality. The current study aimed to develop and evaluate the immunogenicity of inactivated rotavirus vaccine (IRV) in rhesus monkeys. Monkeys received two or three IRV injections intramuscularly at a 4-week interval. Neutralizing antibodies, cellular immunity, PBMC gene expression profiling, and immune persistence were evaluated. Three-dose immunization of IRV induced a higher level of neutralizing, IgG and IgA antibodies compared to two-dose immunization. IRV induced IFN-γ secretion to mediate cellular immune responses, including robust pro-inflammatory and antiviral responses. Chemokine-mediated signaling pathways and immune response were broadly activated by IRV injection. The IRV-induced neutralizing antibodies resulting from two doses returned to baseline levels 20 weeks after full immunization, while those resulting from three doses returned to baseline levels 44 weeks after full immunization. Increasing immunization dose and injection number will help to improve IRV immunogenicity and neutralizing antibody persistence.

目的 构建表达严重急性呼吸综合征冠状病毒2(severe acute respiratory symptom coronavirus 2,SARS-CoV-2)Delta突变株S蛋白受体结合域(receptor binding domain,RBD)和N蛋白的重组腺病毒,并进行鉴定.方法 将SARS-CoV-2 RBD和N基因片段分别克隆至pcDNA3.0BA载体上,构建重组质粒pcDNA3.0BA-RBD-N,PCR扩增RBD-CMV-N片段,连接至穿梭载体pShuttle-CMV上,将穿梭质粒pShuttle-RBD-N与pAdeasy-1进行同源重组,获得重组质粒pAdeasy-1-RBD-N,转染HEK293细胞进行重组腺病毒Ad-RBD-N包装,RT-PCR法检测重组腺病毒中RBD和N基因在HEK293细胞中的转录,Western blot和免疫荧光法检测重组腺病毒中RBD和N蛋白的表达.将Ad-RBD-N通过肌肉注射免疫12只雌性BALB/c小鼠,免疫剂量为5 × 109copies/只,免疫后14 d经尾静脉采血,ELISA法检测血清抗体效价.结果 重组腺病毒RBD和N基因能在HEK293细胞中正常转录,RBD和N蛋白能在MA104细胞中正常表达.免疫重组腺病毒的小鼠可产生针对RBD和N蛋白的特异性IgG抗体.结论 成功构建了表达SARS-CoV-2 Delta突变株S蛋白RBD和N蛋白的重组腺病毒,为Delta突变株疫苗的后续研究奠定了基础.

Rotavirus (RV) is a major pathogen causing severe diarrhea in infants and children aged less than 5 years. Vaccination is an economically feasible and effective strategy to prevent rotavirus infections. However, immune efficacy of live vaccines could be interfered by maternal antibodies and pre-existing antibodies of children. To develop an inactivated rotavirus vaccine (IRV), we had previously isolated a wild-type human rotavirus strain ZTR-68-A (G1P[8]) from the fecal samples of infants having severe diarrhea in a region endemic for the presence of this pathogen. In our present study, we assessed whether the presence of maternal and pre-existing antibodies in newborn BALB/c mice affected the immunogenicity of IRV administered to these animals. Our results indicate that maternal antibodies, generated from either vaccine immunization or rotavirus infection, showed partial influence with the immune responses generated by two doses of IRV vaccination. Increasing the number of immunizations can significantly improve the titer of serum neutralizing antibody and a seroconversion rate of up to 100%. In newborn mice, single-virus infection did not elicit detectable levels of serum neutralizing antibodies. After an IRV vaccination, the immune responses of these mice remained unaffected, with no significant differences in titers compared with those of control-group mice. In summary, choosing a suitable immunization dose and dosing frequency is essential for the immune effectiveness of IRV. The results of this study will provide animal experimental support for the IRV clinical research in future.

Live-attenuated rotavirus vaccine has shown low protection in underdeveloped or developing countries. However, the inactivated rotavirus vaccine may have the potential to overcome some of these challenges. In the present study, the immunogenicity and protective efficacy of a bivalent inactivated rotavirus vaccine by parenteral administration were elevated in a neonatal rhesus monkey model. A bivalent inactivated rotavirus vaccine containing G1P[8] (ZTR-68 strain) and G9P[8] (ZTR-18 strain) was administered to pregnant rhesus monkeys twice at an interval of 14 days. Neutralizing antibodies against RV strains ZTR-68, ZTR-18, SA11, WA, UK, and Gottfried emerged in pregnant rhesus monkeys and were transplacentally transmitted to the offspring. In the vaccine group, clinical symptoms of diarrhea, viral load in the gut tissue and histopathological changes were significantly reduced in the neonatal rhesus monkeys following oral challenge with the SA11 strain.

Rotavirus (RV) is the major causes of severe diarrhea in infants and young children under five years of age. There are no effective drugs for the treatment of rotavirus in addition to preventive live attenuated vaccine. Recent evidence demonstrates that microRNAs (miRNAs) can affect RNA virus replication. However, the antiviral effect of miRNAs during rotavirus replication are largely unknown. Here, we determined that miR-7 is upregulated during RV replication and that it targets the RV NSP5 (Nonstructural protein 5). Results suggested that miR-7 affected viroplasm formation and inhibited RV replication by down-regulating RV NSP5 expression. Up-regulation of miR-7 expression is a common regulation method of different G-type RV-infected host cells. Then, we further revealed the antiviral effect of miR-7 in diarrhea suckling mice model. MiR-7 is able to inhibit rotavirus replication in vitro and in vivo. These data provide that understanding the role of cellular miR-7 during rotaviral replication may help in the identification of novel therapeutic small RNA molecule drug for anti-rotavirus.

通过构建重组表达载体pEGFP-VP3,将pEGFP-VP3转染MA104细胞,观察VP3的表达情况和表达的VP3对轮状病毒复制的作用,进一步评价构建方式是否成功。GFP荧光和Western Blot结果显示,pEGFP-VP3转染MA104细胞48 h,重组蛋白VP3表达量最高。通过RV拷贝数和免疫荧光检测病毒的复制情况,结果均显示重组蛋白VP3可促进病毒复制,为后续更加深入地探究VP3的功能及在轮状病毒复制中的作用提供了实验基础。

Identification of a suitable nonhuman primate (NHP) model of COVID-19 remains challenging. Here, we characterized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in three NHP species: Old World monkeys Macaca mulatta (M. mulatta) and Macaca fascicularis (M. fascicularis) and New World monkey Callithrix jacchus (C. jacchus). Infected M. mulatta and M. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight. Viral genomes were detected in swab and blood samples from all animals. Viral load was detected in the pulmonary tissues of M. mulatta and M. fascicularis but not C. jacchus. Furthermore, among the three animal species, M. mulatta showed the strongest response to SARS-CoV-2, including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues. Collectively, these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M. mulatta as the most suitable for modeling COVID-19.

COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Plenty of diagnostic, preventive and therapeutic knowledges have been enriched from clinical studies since December 2019. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines. In this study, two families of non-human primates, Old world monkeys (12 Macaca mulatta , 6 Macaca fascicularis ) and New world monkeys (6 Callithrix jacchus ), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and histopathological examination. Increased body temperature was observed in 100% (12/12) M. mulatta , 33.3% (2/6) M. fascicularis and none (0/6) of C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in nasal swabs, throat swabs, anal swabs and blood from all 3 species of monkeys. Viral shedding from upper respiratory samples reached the peak between day 6 and day 8 post inoculation. From necropsied M. mulatta and M. fascicularis , the tissues showing virus positive were mainly lung, weasand, bronchus and spleen. No viral genome was seen in any of tissues from 2 necropsied C. jacchus. Severe gross lesions and histopathological changes were observed in lung, heart and stomach of SARS-CoV-2 infected animals. In summary, we have established a NHP model for COVID-19, which could be used to evaluate drugs and vaccines, and investigate viral pathogenesis. M. mulatta is the most susceptible to SARS-CoV-2 infection, followed by M. fascicularis and C. jacchus. One Sentence Summary M. mulatta is the most susceptible to SARS-CoV-2 infection as compared to M. fascicularis and C. jacchus .

Background: COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Remarkable achievements have been made in diagnosis, prevention and treatment of COVID-19 from clinical studies. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines. Methods: Two families of three species of non-human primates (NHP), old world monkeys (Macaca mulatta, Macaca fascicularis) and new world monkeys (Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and evaluation of host responses to SARS-CoV-2 infection. Findings: Increased body temperature was observed in M. mulatta and M. fascicularis, but not C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in swab samples and blood from all 3 species of monkeys. Viral shedding from upper respiratory reached the peak between day 6 and day 8 post inoculation. Viruses were mainly detected in lung, weasand, bronchus and spleen of M. mulatta and M. fascicularis, but not C. jacchus. M. mulatta showed stronger cytokine responses to SARS-CoV-2 infection than M. fascicularis. Severe gross lesions and histopathological changes were observed mainly in lung and secondary lymphoid of SARS-CoV-2 infected M. mulatta and M. fascicularis. The susceptibility to SARS-CoV2 infection is M. mulatta > M. fascicularis > C. jacchus. Interpretations: We have established a NHP model for COVID-19, which recapitulates several important aspects of COVID-19 patients and could be used to evaluate anti-viral drugs and vaccines, and investigate viral pathogenesis.Funding Statement: This study was supported by 2020YFC0841100 and 2020YFC0846400. Declaration of Interests: None.Ethics Approval Statement: All animal procedures were approved by the Institutional Animal Care and Use Committee of Institute of Medical Biology, Chinese Academy of Medical Science (Ethics number: DWSP202002 001), and performed in the ABSL-4 facility of National Kunming High-level Biosafety Primate Research Center, Yunnan China.

研究轮状病毒(Rotavirus,RV)非结构蛋白5(NSP5)在体外对RV复制的作用.以质粒pEGFP-N2为载体构建出可特异性表达重组蛋白NSP5的真核表达载体后,将重组质粒转染MA104细胞并分别通过免疫荧光和West-ern Blot检测NSP5在转染后不同时间的表达差异.随后,重组质粒转染组及对照组细胞分别接种相同剂量的RV,一定时间后根据GFP分布来确认重组蛋白NSP5在细胞内的迁移变化情况,并比较实验组和对照组之间的RV复制能力差异.结果发现,NSP5蛋白在重组质粒转染细胞48 h后表达达到顶峰.此外,GFP也显示NSP5蛋白随RV的感染从弥散状转变为点状聚集,且转染该重组质粒的细胞内RV复制水平明显高于对照细胞.说明了轮状病毒NSP5对病毒的复制具有明显促进作用,这也为深入了解RV的感染、复制及致病机理提供理论基础.

The rotavirus (RV) is the most important causative agent of severe gastroenteritis in infants and children aged less than 5 years worldwide. However, the response and the roles of peripheral blood mononuclear cell (PBMC) in RV clearance have yet to be fully elucidated. In this study, we established the neonatal rhesus monkey model of RV infection with histopathological changes in the small intestine. Then, we investigated gene expression changes in PBMCs from the monkey model of RV infection. Similar pathways regulated in rhesus monkeys that received intragastric administration of the RV monkey SA11 strain (G3P[2]) and the human wild‐type strain ZTR‐68 (G1P[8]). Gene profiling showed differences in functional genes mainly associated with chemokine signaling pathways and cytokine‐cytokine receptor interactions post RV infection. Transferrin and C‐C motif chemokine ligand 23 (CCL23) gene expression were upregulated in PBMCs of monkeys when stimulated by simian and human RV strains. Monkeys infected with RV had an enhanced and prolonged inflammatory response that was associated with increased levels of CCL20, CCL23, and C‐X‐C motif chemokine ligand 1; while inhibition of major histocompatibility complex class I expression may be important for immune evasion by RV. The RV infection was also characterized by pathological changes in the small intestine with a cytokine and chemokine storm. This study identified the chemokine signaling pathway and immune response genes involved in RV infection in infant rhesus monkeys. The SA11 RV strain is more suitable for establishing a monkey diarrhea model than the ZTR‐68 RV strain.