Viral immunology最新文献

HIV-infected (HIV⁺) aging adult individuals who have achieved undetectable viral load and improved CD4 T cell counts due to long-term antiretroviral therapy (ART) may continue to experience inflammation and immunosenescence. Therefore, we evaluated the plasma levels of proinflammatory and anti-inflammatory cytokines in 173 HIV⁺ aging adult individuals with age ranging from 22 to 81 years on long-term ART with viral load mostly <20 HIV RNA copies/mL and compared with 92 HIV-uninfected (HIV^- or healthy controls) aging individuals. We found that the median levels of TNF-α, IFN-γ, IL-1β, IL-6, and IL-10 were higher (p < 0.001 to <0.0001) and IL-17 trended lower in HIV⁺ individuals than healthy controls. Increasing CD4 T cell counts in the HIV⁺ cohort did not significantly change the circulating cytokine levels, although levels of IL-1β increased. However, IL-17 levels significantly decreased with increasing CD4 counts in the healthy controls and yet unchanged in the HIV⁺ cohort. Of note, the levels of circulating IL-17 were significantly reduced comparatively in the healthy controls where the CD4 count was below 500, yet once above 500 the levels of CD4, IL-17 levels were comparable with the HIV⁺ cohort. With increasing CD8 T cell counts, the levels of these cytokines were not significantly altered, although levels of TNF-α, IFN-γ, and IL-6 declined, whereas IL-1β and IL-17 were slightly elevated. Furthermore, increasing age of the HIV⁺ cohort did not significantly impact the cytokine levels although a slight increase in TNF-α, IL-6, IL-10, and IL-17 was observed. Similarly, these cytokines were not significantly modulated with increasing levels of undetectable viral loads, whereas some of the HIV⁺ individuals had higher levels of TNF-α, IFN-γ, and IL-1β. In summary, our findings show that HIV⁺ aging adult individuals with undetectable viral load and restored CD4 T cell counts due to long-term ART still produce higher levels of both proinflammatory and anti-inflammatory cytokines compared with healthy controls, suggesting some level of inflammation.

Coronavirus disease 2019 (COVID-19) represented an international health risk. Variants of the interferon-induced transmembrane protein-3 (IFITM3) gene can increase the risk of developing severe viral infections. This cross-sectional study investigated the association between IFITM3 rs12252A>G single nucleotide polymorphism (SNP) and COVID-19 severity and mortality in 100 Egyptian patients. All participants were subjected to serum interleukin-6 (IL-6) determination by ELISA and IFITM3 rs12252 genotyping by real-time polymerase chain reaction. Of all participants, 85.0% had the IFITM3 rs12252 homozygous AA genotype, whereas 15.0% had the heterozygous AG genotype. None of our participants had the homozygous GG genotype. The IFITM3 rs12252A allele was found in 92.5% and the G allele in only 7.5%. There was no significant association (p > 0.05) between the IFITM3 rs12252 SNP and COVID-19 severity, intensive care unit (ICU) admission, or IL-6 serum levels. The heterozygous AG genotype frequency showed a significant increase among participants who died (32.0%) compared with those who had been cured (9.3%). The mutant G allele was associated with patients' death. Its frequency among cured participants was 8.5%, whereas in those who died was 24.2% (p = 0.024) with 3.429 odds ratio [95% confidence interval: 1.1-10.4]. In conclusion, this study revealed a significant association between the G allele variant of IFITM3 rs12252 and COVID-19 mortality. However, results were unable to establish a significant link between rs12252 polymorphism, disease severity, ICU admission, or serum IL-6 levels.

COVID-19, caused by the SARS-CoV-2 virus, can have neurological effects, including cognitive symptoms like brain fog and memory problems. Research on the neurological effects of COVID-19 is ongoing, and factors such as inflammation, disrupted blood flow, and damage to blood vessels may contribute to cognitive symptoms. Notably, some authors and existing evidence suggest that the SARS-CoV-2 virus can enter the central nervous system through different routes, including the olfactory nerve and the bloodstream. COVID-19 infection has been associated with neurological symptoms such as altered consciousness, headaches, dizziness, and mental disorders. The exact mechanisms and impact on memory formation and brain shrinkage are still being studied. This review will focus on pathways such as the olfactory nerve and blood-brain barrier disruption, and it will then highlight the interactions of the virus with different cell types in the brain, namely neurons, astrocytes, oligodendrocytes, and microglia.

Herpesvirus of turkey (HVT) increases activation of T cells in 1-day-old chickens when administered in ovo. This study evaluated whether adding cytosine-guanosine oligodeoxynucleotides (CpG ODNs) to the HVT vaccine could enhance the adjuvant effect of HVT. We used a CpG ODN dose of 10 μg per egg. The experimental groups were (1) diluent-only control (sham), (2) HVT, (3) HVT+CpG ODN, (4) HVT+non-CpG ODN, (5) CpG ODN, and (6) non-CpG ODN control. Cellular response evaluation included measuring the frequencies of macrophages (KUL01⁺MHC-II⁺), gamma delta T cells (γδTCR⁺MHC-II⁺), CD4⁺, and CD8⁺ T cell subsets, including double-positive (DP) cells. In addition, CD4⁺ and CD8⁺ T cell activation was evaluated by measuring the cellular expression of major histocompatibility complex class II (MHC-II), CD44 or CD28 costimulatory molecules. An adjuvant effect was considered when HVT+CpG ODN, but not HVT+non CpG ODN, or CpG ODN, or non-CpG ODN, induced significantly increased effects on any of the immune parameters examined when compared with HVT. The findings showed that (1) HVT vaccination induced significantly higher frequencies of γδ⁺MHC-II⁺ and CD4⁺CD28⁺ T cells when compared with sham chickens. Frequencies of DP and CD4⁺CD28⁺ T cells in HVT-administered birds were significantly higher than those observed in the non-CpG ODN group. (2) Groups receiving HVT+CpG ODN or CpG ODN alone were found to have significantly increased frequencies of activated CD4⁺ and CD8⁺ T cells, when compared with HVT. Our results show that CpG ODN administration in ovo with or without HVT significantly increased frequencies of activated CD4⁺ and CD8⁺ T cells.

Nasopharyngeal carcinoma (NPC) is a specific human malignancy with unique geographic distribution and genetic backgrounds. Although early treatment with radio-chemotherapy has been proven effective for NPC therapy, its therapeutic efficacy substantially diminishes in the late stages of this malignancy. In the tumor microenvironment of NPC, PD-L1 has been demonstrated as a critical factor in impairing T cell activation. As an etiological role for NPC development, it is found that Epstein-Barr virus (EBV) latent proteins upregulated PD-L1 expression. However, whether EBV lytic protein affects PD-L1 expression remains unclear. In this study, through monitoring the mRNA expression pattern of lytic genes and PD-L1 in EBV-positive NPC cell line NA, EBV immediately-early gene BRLF1(Rta) was found to have the potential for PD-L1 activation. Furthermore, we identified that Rta expression enhanced PD-L1 expression in mRNA and protein levels through quantitative real-time polymerase chain reaction and western blotting analysis. The luciferase reporter assay revealed that Rta expression enhanced PD-L1 promoter activity. We also demonstrated that Rta-induced PD-L1 expressions could impair interleukin 2 secretion of T cells, and this mechanism may be through ERK activation. These results displayed the importance of EBV Rta in PD-L1 expression in NPC and may give an alternative target for NPC therapy.

Coronavirus Disease 2019 (COVID-19) is generally susceptible to the population, highly infectious, rapidly transmitted, and highly fatal. There is a lack of specific drugs against the virus at present and vaccination is the most effective strategy to prevent infection. However, studies have found that some groups, particularly patients with diabetes, show varying degrees of weak immune reactivity to various COVID-19 vaccines, resulting in poor preventive efficacy against the novel coronavirus in patients with diabetes. Therefore, in this study, patients with type 2 diabetes mellitus (T2DM) who had weak immune response to the COVID-19 vaccine in recent years were analyzed. This article reviews the phenomenon, preliminary mechanism, and related factors affecting weak vaccine response in patients with T2DM, which is expected to help in the development of new vaccines for high-risk groups for COVID-19.

Hepatitis B virus (HBV) is a global public health concern, and China continues to face a high burden of HBV cases. Vaccination plays a critical role in controlling and eradicating HBV. However, studies have shown that some individuals may experience waning immunity over time, highlighting the importance of enhanced immunization strategies. This study aimed to investigate the relationship between age, gender, and anti-HBs antibody levels, as well as the prevalence of serum hepatitis B surface antigen (HBsAg)/HBV e antigen (HBeAg) positivity. This retrospective study included 43,609 pediatric patients who visited the outpatient department between January 2013 and December 2022. Serum biomarkers (HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc) were measured using Roche Cobas 8000. There is a significant difference in anti-HBs titer between genders and across different age groups (p < 0.05). The serological markers HBsAg/HBeAg exhibited the highest positivity rate in the age group of 15-18 years. The findings demonstrate a gradual decrease in anti-HBs levels following HBV vaccination. The prevalence of serum markers HBsAg/HBeAg is higher among adolescents aged 15-18 years, which should be a matter of concern and attention.

Kyasanur Forest Disease Virus (KFDV) is a tick-borne flavivirus that causes life-threatening hemorrhagic fever in humans with case fatality rates of 3-5%. Relatively little is known about the mechanism of its pathogenesis or host immune responses to KFDV infection. Here, we investigated KFDV-specific cellular immune responses in the recovered cases of Kyasanur Forest Disease (KFD). Peripheral blood mononuclear cells of the recovered KFD cases and healthy controls were exposed to γ-inactivated KFDV antigen ex vivo. The proliferation index was determined using an enzyme-linked immunosorbent assay-based lymphoproliferative assay. The frequencies of CD4⁺ and CD8⁺ T cells expressing intracellular interferon (IFN)-γ in response to stimulation with γ-inactivated KFDV antigen were determined using flow cytometry. A significant increase in lymphoproliferation and a high frequency of CD4⁺ and CD8⁺ T cells secreting IFN-γ against γ-inactivated KFDV antigen were found in the recovered KFD group compared to the healthy control group. In conclusion, the study indicated the generation of cellular immune responses in individuals who recovered from KFD and can be used as indicators of cellular immunity in KFD vaccine studies.

The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a vaccine against RSV has been a priority, and the recently approved Arexvy vaccine has shown promise in preventing lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 years and older. This comprehensive review discusses the history of RSV, challenges in vaccine development, and the mechanism of action of Arexvy. The efficacy and safety of the vaccine are explored based on phase 3 clinical trial, demonstrating its effectiveness in preventing RSV-associated LRTD. The most common adverse reactions reported include injection site pain, fatigue, myalgia, headache, and arthralgia. Ongoing research focuses on the long-term effectiveness of Arexvy, including the need for booster doses and its impact on reducing RSV-associated hospitalizations. The potential of Arexvy to lessen the burden of RSV-related illnesses, particularly in vulnerable populations, is highlighted, emphasizing the importance of widespread immunization efforts and accessibility to this groundbreaking vaccine.