In 2017, a survey of the molecular epidemiology of human adenovirus (HAdV) infections in Southern China based on hexon and fiber genotype demonstrated that the most prevalent genotypes of HAdV were HAdV-3 (n = 62), HAdV-2 (n = 21), and HAdV-7 (n = 16). In addition, two patients were co-infected with two genotypes of HAdV. Interestingly, a novel human adenovirus C recombinant genotype strain was isolated from one of the pneumonia patients in this survey. Phylogenetic, recombination, and proteotyping analysis showed that this novel pathogen originated from the recombination of parental viruses harboring the HAdV-1 penton and hexon gene, and the HAdV-2 fiber gene. It was named ‘P1H1F2’ and was assigned as HAdV-C104 based on the nomenclature protocol of using three major capsid proteins for characterization. Subsequent in vitro experiments demonstrated that HAdV-C104 had comparable proliferation capacity to HAdV-1, HAdV-2, and another recombination genotype P1H2F2. In addition, the HAdV-C104 infected patient was diagnosed with pneumonia and recovered after antiviral therapy. This report strengthens the hypothesis of recombination as a major pathway for the molecular evolution of HAdV-C species.
Nasopharyngeal carcinoma (NPC) is common in Southern China. The molecular mechanism underlying NPC genesis and progression has been comprehensively investigated, but the key gene (s) or pathway (s) pertaining to NPC are unidentified. We explored some key genes and pathways involved in NPC through using meta-analysis of deposited expression of microarray data of NPC. The expression of proliferating cell nuclear antigen clamp associated factor (PCLAF) was determined by real-time PCR and western blots. CCK-8 assay, colony formation assay, transwell migration assay, cell wound healing assay, cell cycle analysis and cell apoptosis were carried out to assess biological behaviors caused by downregulation and overexpression of PCLAF in vitro. CHIP was utilized to determine the direct upstream regulatory transcription factors of PCLAF. PCLAF was the key gene of NPC, which was significantly up-regulated in NPC cell line compared to the normal nasopharyngeal cell line. Additionally, in vitro assay has demonstrated the down-regulation and overexpression of PCLAF, resulted in significantly suppressed and enhanced NPC proliferation, metastasis and invasion respectively. Furthermore, the up-regulation of PCLAF in NPC is induced by direct binding of dysregulated NF-κB p50/RelB complex to the promoter of PCLAF. Our results offer a strategy for re-using the deposited data to find the key genes and pathways involved in pathogenesis of cancer. Our study has provided evidence of supporting the role of PCLAF in NPC genesis and progression.
Homologous booster, heterologous booster, and Omicron variants breakthrough infection (OBI) could improve the humoral immunity against Omicron variants. Questions concerning about memory B cells (MBCs) and T cells immunity against Omicron variants, features of long-term immunity, after booster and OBI, needs to be explored. Here, comparative analysis demonstrate antibody and T cell immunity against ancestral strain, Delta and Omicron variants in Omicron breakthrough infected patients (OBIPs) are comparable to that in Ad5-nCoV boosted healthy volunteers (HVs), higher than that in inactivated vaccine (InV) boosted HVs. However, memory B cells (MBCs) immunity against Omicron variants was highest in OBIPs, followed by Ad5-nCoV boosted and InV boosted HVs. OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs, and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs. Collectively, these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.