{"title":"Immunosenescence and Inflammaging in COVID-19.","authors":"Faezeh Asghari, Amir Asghary, Naime Majidi Zolbanin, Fatemeh Faraji, Reza Jafari","doi":"10.1089/vim.2023.0045","DOIUrl":"10.1089/vim.2023.0045","url":null,"abstract":"<p><p>Despite knowledge gaps in understanding the full spectrum of the hyperinflammatory phase caused by SARS-CoV-2, according to the World Health Organization (WHO), COVID-19 is still the leading cause of death worldwide. Susceptible people to severe COVID-19 are those with underlying medical conditions or those with dysregulated and senescence-associated immune responses. As the immune system undergoes aging in the elderly, such drastic changes predispose them to various diseases and affect their responsiveness to infections, as seen in COVID-19. At-risk groups experience poor prognosis in terms of disease recovery. Changes in the quantity and quality of immune cell function have been described in numerous literature sites. Impaired immune cell function along with age-related metabolic changes can lead to features such as hyperinflammatory response, immunosenescence, and inflammaging in COVID-19. Inflammaging is related to the increased activity of the most inflammatory factors and is the main cause of age-related diseases and tissue failure in the elderly. Since hyperinflammation is a common feature of most severe cases of COVID-19, this pathway, which is not fully understood, leads to immunosenescence and inflammaging in some individuals, especially in the elderly and those with comorbidities. In this review, we shed some light on the age-related abnormalities of innate and adaptive immune cells and how hyperinflammatory immune responses contribute to the inflammaging process, leading to clinical deterioration. Further, we provide insights into immunomodulation-based therapeutic approaches, which are potentially important considerations in vaccine design for elderly populations.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"579-592"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potent Antibody Response Elicited by a Third Booster Dose of Inactivated COVID-19 Vaccine in Healthy Subjects.","authors":"Ruili Ji, Jiaqi Zhang, Dan Liang, Hongbing Quan, Yue Wu, Aiping Peng, Weili Li, Shaofang Lu, Xuedong Zhang, Changwen Ke, Dawei Wang, Jianhua Xu","doi":"10.1089/vim.2023.0072","DOIUrl":"10.1089/vim.2023.0072","url":null,"abstract":"<p><p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has been used worldwide on a large scale because of its potent ability to contain the coronavirus disease 2019 (COVID-19) pandemic, and the antibody response induced by the vaccine needs to be elucidated. Thus, we conducted a prospective trial in healthy subjects to observe the antibody response after three doses of inactivated vaccines. Our results showed that neutralizing antibody (NAb) levels were significantly higher after the booster vaccination compared to the second, a 4.9-fold increase, with the peak occurring at 28 days. The NAb level could be maintained for a longer period after the third vaccination, with higher levels still observed after 3 months. We did not observe significantly higher levels of SARS-CoV-2 spike-specific immunoglobulin G (S-IgG) and immunoglobulin M (IgM) after the third vaccination compared with the second vaccination; this was especially true for SARS-CoV-2 spike-specific immunoglobulin M (S-IgM), which was barely expressed. Notably, those who did not undergo NAb seroconversion after two doses of the vaccine produced high and long-lasting NAb after the third vaccination, confirming that they were not completely unresponsive to the vaccine. The NAb titer in younger subjects (aged 20-40 years) rose 3.4-fold compared with older subjects (aged 40-60 years) after the second vaccination, but the difference was narrowed after the third vaccination (2.8-fold increase). In addition, the levels of antibodies in older men were 3.4-fold lower than those in the older women after the third vaccination. Overall, this study elucidates the dynamic change in antibodies after three doses of vaccination, which provides a reference for the improvement of vaccination strategies.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"593-599"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41171685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viral immunologyPub Date : 2023-11-01Epub Date: 2023-10-13DOI: 10.1089/vim.2023.0060
Mahmoud M Bahgat, Rola Nadeem, Mohamed H Nasraa, Khaled Amer, Wael A Hassan, Fadya M ELGarhy, Salem Reda, Dina N Abd-Elshafy
{"title":"Proinflammatory Cytokine Profiles in Both Mild Symptomatic and Asymptomatic SARS-CoV-2-Infected Egyptian Individuals and a Proposed Relationship to Post-COVID-19 Sequela.","authors":"Mahmoud M Bahgat, Rola Nadeem, Mohamed H Nasraa, Khaled Amer, Wael A Hassan, Fadya M ELGarhy, Salem Reda, Dina N Abd-Elshafy","doi":"10.1089/vim.2023.0060","DOIUrl":"10.1089/vim.2023.0060","url":null,"abstract":"<p><p>Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with proinflammatory cytokine release as mediators of host antiviral response to the infection. Cytokine persistent elevation leads to post-Coronavirus disease-2019 (COVID-19) post-COVID-19 sequela (PCS) reported in about 60% of patients affecting individual's normal life after recovery. This study evaluates relationship of cytokines and chemokines pattern during and postinfection to PCS events. Serum samples collected from 82 individuals with symptomatic, asymptomatic, or no SARS-CoV-2 infection were classified as recently or formerly infected groups according to levels of anti-2019nCoV Immunoglobulin G/Immunoglobulin M. Levels of interleukin (IL)-1<i>α</i>, IL-1<i>β</i>, IL-6, IL-8, interferon alpha (IFN-<i>α</i>), tumor necrosis factor alpha (TNF-<i>α</i>), granulocyte macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein-1 were assessed via ELISA for each individual. All asymptomatic groups showed nonsignificant differences in cytokines' levels than control group. Significant elevation of IFN-<i>α</i>, TNF-<i>α</i>, and GM-CSF levels were observed in recent symptomatic, while IFN-<i>α</i> and TNF-<i>α</i> levels were significant in former symptomatic groups. We observed an association between fever with IL-1<i>α</i> and IFN-<i>α</i> levels, fatigue with TNF-<i>α</i> and GM-CSF, dyspnea with IFN-<i>α</i>, TNF-<i>α</i>, and GM-CSF, and chest-wheezing with GM-CSF. Individuals were surveyed 12 months postsampling for PCS events. Among 35 responders to survey, 8 (22.8%) reported PCS events, 6 of which were females. Upon studying PCS events, IL-8, IFN-<i>α</i>, TNF-<i>α</i>, and GM-CSF levels showed significant elevation in active infection, that was not seen in a resolved state of infection. Cytokines patterns suggest that either a persistent elevation in levels or damage caused during infection contributes to PCS. Although with the limited sample size, our study emphasizes the importance to conduct medical approaches targeting the associated cytokines to improve the PCS symptoms.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"600-609"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41214339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viral immunologyPub Date : 2023-11-01DOI: 10.1089/vim.2023.0126.editorial
Rodney S Russell
{"title":"Continuing to Learn About COVID-19.","authors":"Rodney S Russell","doi":"10.1089/vim.2023.0126.editorial","DOIUrl":"10.1089/vim.2023.0126.editorial","url":null,"abstract":"","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":"36 9","pages":"563"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107592378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viral immunologyPub Date : 2023-11-01Epub Date: 2023-09-26DOI: 10.1089/vim.2023.0077
Fang Li, Biao Song, Wei-Feng Zhou, Li-Jin Chu
{"title":"Toll-Like Receptors 7/8: A Paradigm for the Manipulation of Immunologic Reactions for Immunotherapy.","authors":"Fang Li, Biao Song, Wei-Feng Zhou, Li-Jin Chu","doi":"10.1089/vim.2023.0077","DOIUrl":"10.1089/vim.2023.0077","url":null,"abstract":"<p><p>The innate immune system recognizes conserved features of viral and microbial pathogens through pattern recognition receptors (PRRs). Toll-like receptors (<i>TLR</i>s) are one type of PRR used by the innate immune system to mediate the secretion of proinflammatory cytokines and promote innate and adaptive immune responses. <i>TLR</i> family members <i>TLR</i>7 and TLR8 (referred to as <i>TLR</i>7/8 from herein) are endosomal transmembrane receptors that recognize purine-rich single-stranded RNA (ssRNA) and bacterial DNA, eliciting an immunologic reaction to pathogens. <i>TLR</i>7/8 were discovered to mediate the secretion of proinflammatory cytokines by activating immune cells. In addition, accumulating evidence has indicated that TLR7/8 may be closely related to numerous immune-mediated disorders, specifically several types of cancer, autoimmune disease, and viral disease. <i>TLR</i>7/8 agonists and antagonists, which are used as drugs or adjuvants, have been identified in preclinical studies and clinical trials as promising immune stimulators for the immunotherapy of these immune-mediated disorders. These results provided reasoning to further explore immunotherapy for the treatment of immune-mediated disorders. Nevertheless, numerous needs remain unmet, and the therapeutic effects of <i>TLR</i>7/8 agonists and antagonists are poor and exert strong immune-related toxicities. The present review aimed to provide an overview of the <i>TLR</i> family members, particularly <i>TLR</i>7/8, and address the underlying molecular mechanisms and clinical implications of <i>TLR</i>7/8 in immune-mediated disorders. The aim of the work is to discuss the underlying molecular mechanisms and clinical implications of <i>TLR</i>7/8 in immune-mediated disorders.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"564-578"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41156394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression Pattern of Cholesterol 25-Hydroxylase and Serum Level of 25-Hydroxycholesterol and Relevant Inflammatory Cytokines in Patients with Varying Disease Severity of COVID-19.","authors":"Mona Roozbehani, Mohammad Hossein Razizadeh, Hossein Keyvani, Fatemeh Nejati, Sharareh Soleymani, Leila Mousavizadeh","doi":"10.1089/vim.2023.0051","DOIUrl":"10.1089/vim.2023.0051","url":null,"abstract":"<p><p>Cholesterol 25-hydroxylase (<i>CH25H</i>) and its product 25-hydroxycholesterol (25HC) showed antiviral effects against various viruses <i>in vitro</i>. <i>CH25H</i> expression is regulated in mice by pro-inflammatory cytokine interferons (IFNs) in mice but data on its possible correlation with IFNs in humans are still unclear. We examined gene expression of <i>CH25H</i>, <i>IFN</i>-<i>α</i>, and <i>IFN</i>-<i>β</i> and serum levels of 25HC in Iranian patients with mild and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Fifty intensive care unit (ICU) patients and outpatients with SARS-CoV-2 and 25 healthy controls were studied. Gene expression of <i>CH25H</i> and relevant inflammatory cytokines was quantified in peripheral blood mononuclear cells by real-time polymerase chain reaction. The expression of <i>CH25H</i> and serum levels of 25HC were significantly higher in ICU patients with SARS-CoV-2. Notably, <i>IFN</i>-<i>α</i> levels increased in healthy controls. However, compared to healthy controls, <i>IFN</i>-<i>β</i> was considerably higher in outpatients. Finally, statistical analysis shows that no correlation was found between <i>CH25H</i> and <i>IFN</i>-<i>α</i> expression; nevertheless, a lower correlation was found with <i>IFN</i>-<i>β</i>. The data revealed that <i>CH25H</i> and 25HC levels increase after SARS-CoV-2 infection. In other words, decreased levels of those factors in severe patients compared with mild patients may indicate the importance of their function in controlling the progression of the disease.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"610-616"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41214338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterization of Pre-Existing Neutralizing Antibody to Human Adenovirus Types 5 and 49 and Simian Type 23 in Chinese Population.","authors":"Peng Zou, Qi Wang, Panli Zhang, Shengxue Luo, Cong Wang, Enhui Zhang, Ling Zhang, Chengyao Li, Tingting Li","doi":"10.1089/vim.2023.0023","DOIUrl":"10.1089/vim.2023.0023","url":null,"abstract":"<p><p>Recombinant adenovirus vector has been widely used in vaccine development. Due to the pre-existing immunity of human adenovirus type 5 (HAd5) in humans, a range of rare human and chimpanzee adenovirus vectors have been developed. In the previous study, we constructed novel adenovirus vector Sad23L and Ad49L based on simian adenovirus type 23 (SAd23) and human adenovirus type 49 (HAd49), which were used in the development of ZIKV and COVID-19 vaccines. However, the levels of pre-existing neutralizing antibody (NAb) of HAd49 and SAd23 remain unclear in China. In this study, we measured NAbs titers of HAd5, HAd49, and SAd23 in 600 healthy blood donors from 6 regions across China. NAb titer of HAd49 or SAd23 was significantly lower than that of HAd5 (<i>p</i> < 0.001). There was no significant difference in seroprevalence and NAb titers of three adenoviruses between male and female donors. The seropositive rates of HAd5 and SAd23 increased with age growth in a positive correlation (<i>p</i> < 0.01), while in contrast to HAd5, HAd49, and SAd23 had a low level of pre-existing immunity in Chinese population, which suggested that Ad49L and Sad23L vectors could be used in vaccine development for humans.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"617-625"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viral immunologyPub Date : 2023-10-01Epub Date: 2023-08-21DOI: 10.1089/vim.2023.0012
Miguel A Fernández-Rojas, Guillermina Ávila, Mirza Romero-Valdovinos, Tanya Plett-Torres, Ana María Salazar, Monserrat Sordo, Mariana Chávez-Vargas, Cesar Josué Coeto Ángeles, Mayra Cruz-Rivera, Carlos Santiago-Olivares, Juan Pablo Ramírez Hinojosa, Pablo Maravilla, Ana Flisser, Patricia Ostrosky-Wegman, Fela Mendlovic
{"title":"Elevated Levels of Cytotoxicity, Cytokines, and Anti-SARS-CoV-2 Antibodies in Mild Cases of COVID-19.","authors":"Miguel A Fernández-Rojas, Guillermina Ávila, Mirza Romero-Valdovinos, Tanya Plett-Torres, Ana María Salazar, Monserrat Sordo, Mariana Chávez-Vargas, Cesar Josué Coeto Ángeles, Mayra Cruz-Rivera, Carlos Santiago-Olivares, Juan Pablo Ramírez Hinojosa, Pablo Maravilla, Ana Flisser, Patricia Ostrosky-Wegman, Fela Mendlovic","doi":"10.1089/vim.2023.0012","DOIUrl":"10.1089/vim.2023.0012","url":null,"abstract":"Current evidence shows higher production of cytokines and antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) in severe and critical cases of Coronavirus Disease 2019 (COVID-19) in comparison with patients with moderate or mild disease. A recent hypothesis proposes an important role of genotoxicity and cytotoxicity in the induction of the cytokine storm observed in some patients at later stages of the disease. Interestingly, in this study, we report significantly higher levels of interleukin (IL)-1β, IL-6, MCP-1, and IL-4 cytokines in mild COVID-19 patients versus severe cases, as well as a high frequency of karyorrhexis (median [Me] = 364 vs. 20 cells) and karyolysis (Me = 266 vs. 52 cells) in the mucosal epithelial cells of both groups of patients compared with uninfected individuals. Although we observed higher levels of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients, IgM antibodies were significantly higher only in mild cases, for the N and the S viral antigens. High levels of IgG antibodies were observed in both mild and severe cases. Our results showed elevated concentrations of proinflammatory and anti-inflammatory cytokines in mild cases, which may reflect an active innate immune response and could be related to the higher IgM and IgG antibody levels found in those patients. In addition, we found that SARS-CoV-2 infection induces cytotoxic damage in the oral mucosa, highlighting the importance of studying the genotoxic and cytotoxic events induced by infection and its role in the pathophysiology of COVID-19.","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"550-561"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10173677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of Immunogenicity of Alum and MF59-Like Adjuvant Inactivated SARS-CoV-2 Vaccines Against SARS-CoV-2 Variants in Elderly Mice.","authors":"Shuang Bai, Yanli Kang, Weixin Chen, Hui Xie, Lichi Zhang, Min Lv, Jian Wang, Jiang Wu, Wei Zhao","doi":"10.1089/vim.2023.0041","DOIUrl":"10.1089/vim.2023.0041","url":null,"abstract":"<p><p>The constant emergence of variants of concern (VOCs) challenges the effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines over time. This is most concerning in clinically vulnerable groups, such as older adults. This study aimed to determine whether the novel adjuvant MF59-like adjuvant can improve cross-immunity against VOCs in aged animals. We compared the humoral and cellular immune responses of Alum and MF59-like adjuvant-formulated inactivated coronavirus disease 2019 (COVID-19) vaccines against prototype and SARS-CoV-2 variants in 18-month-old mice. Our results showed that two doses of the MF59-like adjuvant inactivated vaccines induced more robust binding and pseudo-neutralizing antibodies (Nabs) against the SARS-CoV-2 prototype and VOCs compared to the Alum-adjuvant and reduced Omicron variant escapes from Nabs in aged mice. The humoral immune responses of inactivated vaccines were much lower against VOCs than the prototype with or without adjuvants; however, T cell responses against VOCs were not affected. In addition, Alum and MF59-like adjuvanted vaccines induced Th1-biased immune responses with increased interferon-gamma and interleukin (IL)-2 secreting cells, and hardly detectable IL-4 and IL-5. Furthermore, the MF59-like adjuvant vaccine produced 1.9-2.0 times higher cross-reactive T cell responses against the SARS-CoV-2 prototype and VOCs than the Alum adjuvant. Therefore, our data have important implications for vaccine adjuvant strategies against SARS-CoV-2 VOCs in older adults.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"526-533"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10128341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Altered Vitamin D Receptor Expression in <i>Apa-I</i> (rs7975232) Allelic Variants-A Probable Risk Factor for Susceptibility to Hepatitis B Virus Infection and Disease Progression.","authors":"Manash Jyoti Kalita, Simanta Kalita, Partha Pratim Das, Gautam Hazarika, Kalpajit Dutta, Ankur Jyoti Deka, Juchidananda Bhuyan, Md Ghaznavi Idris, Bikash Narayan Choudhury, Harpreet Kaur, Subhash Medhi","doi":"10.1089/vim.2023.0057","DOIUrl":"10.1089/vim.2023.0057","url":null,"abstract":"<p><p>Vitamin D exerts its antiviral effect through vitamin D receptor (VDR)/retinoid X receptor-mediated host immunomodulation. Besides the downregulation of VDR expression, its polymorphism was also observed among hepatitis B virus (HBV)-positive patients. To understand the possible link between VDR polymorphism and its altered expression during HBV infection and disease progression, VDR <i>Apa-I</i> [rs7975232 (C>A)] single nucleotide polymorphism (SNP) was analyzed in a case-control manner. VDR <i>Apa-I</i> (rs7975232, C>A) polymorphism was studied using 340 HBV patients and 102 healthy controls. Genotype analysis and gene expression study was performed using restriction fragment length polymorphism and quantitative polymerase chain reaction, respectively. Statistical analysis was performed using SPSS (IBM) considering <i>p</i>-value <0.05 as significant for comparing the differences between the groups. Significant mean difference in VDR expression was observed between HBV-positive patients (1.6 ± 0.94) and controls (0.69 ± 0.73). Furthermore, the mean fold change of Healthy control with CC genotype (1.92 ± 0.99) was found to be marginally significant compared with mutant genotype (CA/AA) (1.08 ± 0.43/0.59 ± 0.56, <i>p</i> = 0.045). In HBV+ patients, the mean fold change in the CC genotype was 0.88 ± 0.38, which exhibits a significant mean difference upon comparison with other genotypes (0.52 ± 0.49, 0.113 ± 0.34; <i>p</i> = 0.018, <i>p</i> = 0.048). However, the fold change value does not differ between CA and AA genotypes. Further comparative analysis of VDR expression between the control and case also exhibits significant differences (<i>p</i> = 0.001) among allelic variants. Observed genotype distribution frequency exhibits a significant association with disease type. The mutant genotype was found to be significantly associated with HBV infection and disease progression, (odds ratio = 0.730, 95% confidence interval = 0.462-1.152, <i>p</i> = 0.06). VDR SNP rs7975232 (C>A) may affect VDR expression by controlling several other variables and suggest that deviation from wild-type genotype (CC) is associated with downregulation of expression, which in turn involved in host immunomodulation in favor of HBV infection and disease progression.</p>","PeriodicalId":23665,"journal":{"name":"Viral immunology","volume":" ","pages":"534-543"},"PeriodicalIF":2.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10146109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}