Human cytomegalovirus (HCMV) profoundly reprograms host transcription and RNA metabolism, yet its impact on transcription start site (TSS) regulation of host genes remains poorly understood. Here, we employed NanoCap Analysis of Gene Expression sequencing (NanoCAGE-seq) to investigate HCMV-driven changes in alternative TSS usage across the host transcriptome. We identified widespread TSS switching, with ribosomal protein genes (RPGs) emerging as a highly enriched category. Alternative TSS usage produced isoforms with distinct 5’untranslated regions (UTRs), thereby altering cis-regulatory elements that shape translational efficiency. Integrative transcriptomic and proteomic analyses revealed a paradoxical accumulation of RPG proteins despite transcriptional downregulation during infection. Using 5’ Rapid Amplification of cDNA Ends (5’RACE), we characterized four RPGs of RPL4, RPS11, RPS23, and RPS24 that generated 5’UTR variants through alternative TSS usage. Notably, isoforms containing a 5’terminal oligopyrimidine (5’TOP) motif were significantly enriched, correlating with mTOR activation induced by HCMV. Functional assays with bicistronic reporter constructs in HEK293 cells and infection models in human embryonic lung fibroblasts demonstrated that the RPL4 5’TOP isoform exhibited enhanced mTORC1-driven translation compared with non-5’TOP counterparts. Importantly, RPL4 upregulation facilitated viral protein synthesis and boosted production of infectious virions. Together, our findings reveal that dynamic TSS switching of RPGs provides a simple, yet effective, mechanism for fine-tuning mTORC1-responsive translation. By co-opting host transcriptional and translational programs, HCMV enhances ribosome function to optimize the cellular environment for productive viral replication.

The eukaryotic ribosome is a large ribonucleoprotein complex consisting of four types of ribosomal RNA (rRNA) and approximately 80 ribosomal proteins (RPs), forming the 40S and 60S subunits. In all living cells, its primary function is to produce proteins by converting messenger RNA (mRNA) into polypeptides. In addition to their canonical role in protein synthesis, RPs are crucial in controlling vital cellular processes such as cell cycle progression, cellular proliferation, differentiation, DNA damage repair, genome structure maintenance, and the cellular stress response. Viruses, as obligate intracellular parasites, depend completely on the machinery of the host cell for their replication and survival. During viral infection, RPs have been demonstrated to perform a variety of extra-ribosomal activities, which are especially important in viral disease processes. These functions cover a wide range of activities, ranging from controlling inflammatory responses and antiviral immunity to promoting viral replication and increasing viral pathogenicity. Deciphering the regulatory mechanisms used by RPs in response to viral infections has greatly expanded our understanding of their functions outside of the ribosome. Furthermore, these findings highlight the promising role of RPs as targets for the advancement of antiviral therapies and the development of novel antiviral approaches. This review comprehensively examines the many functions of RPs outside of the ribosome during viral infections and provides a foundation for future research on the host–virus interaction.

目的 了解沈阳地区不同年龄段患者中人巨细胞病毒?(HCMV)?的感染状况.方法 选择疑似HCMV感染患者123616例,采用荧光定量PCR技术检测HCMV?DNA,化学发光免疫分析法检测血清HCMV?IgM和IgG抗体,收集患者临床诊断信息.结果 HCMV?DNA、IgM抗体、IgG抗体阳性率分别为12.48％、2.34％、95.58％.>28?d～1岁组患儿HCMV?DNA阳性率?(31.52％)、IgM抗体阳性率?(9.86％)?最高.不同体液HCMV?DNA阳性率不同,尿HCMV?DNA阳性率?(14.61％)?大于血清?(2.36％)?和肺泡灌洗液?(2.17％).HCMV?DNA阳性率与IgM抗体阳性率呈正相关,HCMV?DNA阳性患者中,HCMV?IgM抗体阳性者病毒载量高于IgM抗体阴性者.HCMV感染的临床诊断包括肺炎、神经系统损害、肝炎、血液病等.结论 不同年龄段患者的HCMV感染状况存在差异.婴儿是HCMV易感人群,HCMV感染后主要累及肺脏、肝脏、神经系统等.多种体液样本HCMV?DNA检测以及HCMV?DNA与IgM抗体联合检测对HCMV检测和诊治有重要的意义.

目的 探讨沈阳地区手足口病病原体分布及流行特征,为手足口病的防控和临床诊治提供参考依据.方法 采用描述性流行病学方法,对2014—2018年中国医科大学附属盛京医院就诊的手足口病患儿病例信息及病原学监测数据进行分析.结果 共接诊临床诊断手足口病患儿25571例,17263例(67.51％)肠道病毒检测阳性,其中男患儿阳性检出率为69.72％(10305/14780),女患儿阳性检出率为64.48％(6958/10791),男女患儿阳性检出率比较,差异有统计学意义(χ2=78.167,P<0.001).手足口病肠道病毒检测阳性患儿中,<6岁者占92.59％,其中3～岁年龄组占比最高(24.53％).手足口病全年均有发病,但季节分布明显,呈单峰状分布,每年7、8月份最高,占比为29.94％～52.30％.手足口病分离病原体EV-71占12.71％,CV-A16占24.38％,其他肠道病毒占62.91％.结论 除EV-71和CV-A16外沈阳地区手足口病患儿感染其他肠道病毒所占比例较高,每年7、8月份为手足口病高发期,以<6岁的儿童发病为主,男孩发病居多.

Objective To investigate the distribution of human papillomavirus (HPV) infection characteristics and genotypes in Shenyang area of Liaoning province.Methods HPV genes were detected in cervical exfoliated cells from 55,548 patients by amplification and diversion hybridization.Results A total of 9,566 patients were positive for HPV infection with a positive rate of 17.22％.Additionally,the positive rate of high risk HPV infection was 14.57％ and the positive rate of single genotype HPV infection was 13.63％.Totally,12,360 HPV viruses were detected.Among them,10,879 HPV viruses were classified into high risk genotypes (10,879 out of 12,360,88.02％).The genotypes in women with ages less than 20 were 16/11/6/51/58/52 genotypes;the susceptible HPV genotypes in other women were 16/58/52/53/39/51/81 genotypes.Conclusions HPV infections in Shenyang are mainly infections with high risk viruses and single infection.The infection rate and genotype distribution of HPV are different in different age groups.More suitable HPV vaccine prophylaxis can be taken according to the epidemic characteristics of HPV in this area.

Hypermethylation of the cytosine-phosphate-guanine (CpG) sites located at the 3'-major capsid protein L1 (3'L1) and the long control region (LCR) of the human papillomavirus (HPV) genome may be associated with the progression of cervical cancer (CC). However, the methylation status of the LCR of HPV type 16 DNA remains to be elucidated in an infected Chinese population. The aim of the present study was to investigate the association between methylation of the HPV 16 L1 gene and LCR, and the severity of cervical lesions in infected female patients. Therefore, bisulfite modification, polymerase chain reaction amplification and sequencing were used to analyze 122 HPV 16-positive clinical cervical swabs obtained from patients in northeastern China. The proportion of methylated samples at each of the 7 CpG sites within the 3'-L1/5'-LCR and 5 CpG sites within the promoter region was significantly increased in patients with CC, compared with that observed in high-grade squamous intraepithelial lesions (HSIL) and normal tissue/low-grade intraepithelial lesions (LSIL) (χ2 test, P<0.01). The mean methylation frequencies of the CpG sites 7,089 and 7,143 exhibited an area under the curve value of 0.822 [95% confidence interval (CI)=0.733-0.911] for distinguishing CC from other lesions, 0.787 (95% CI=0.700-0.874) for distinguishing normal/LSIL from HSIL and CC, and 0.763 (95% CI=0.652-0.874) for distinguishing CC from HSIL. These results suggest that the methylation of CpG sites within the HPV 16 3'-L1 and LCR region is correlated with the severity of cervical lesions. Quantification of HPV DNA methylation in the L1 gene and promoter region appears to provide a promising novel marker for distinguishing between normal tissue/LSIL, HSIL and CC in a Chinese population.

Objective To quantifiably measure the methylation frequency of 18 CpG sites in the 3′region of L1 gene and long control region(LCR) gene of HPVl6 DNA,and study the relationship between HPVl6 DNA methylation and severity of cervical lesions. Methods A total of 10 cases Normal/low?grade squamous intraepithelial lesion(Normal/LSIL),10 cases of high?grade squamous intraepithelial lesion(HSIL),and 10 cases of cervical cancer(CC)were recruited for the study. The relationship between severity of cervical lesions and HPV16 DNA methylation was analyzed by bisultlte?pyrosequencing. Results The methylation rate was highest in Normal/LSIL at position 7 089 located in 3′?L1,followed by CC. The low?est was found in HSIL. The difference in methylation percentage among the three lesions was significant(P=0.006). In 7 134,the proportion meth?ylation was also different among three groups(P=0.01),difference in methylation percentage between Normal/LSIL and CC,as well as Normal/LSIL and HSIL was significant(P=0.038,0.017). Conclusion The methylation status of CpG sites 7 089 and 7 134 in the 3′region of L1gene is asso?ciated with the severity of cervical disease. The quantification of HPV DNA methylation can be used for cervical disease screening in clinical samples.