Search Results (598)

Simian foamy virus (SFV) is a retrovirus that infects primates. However, epidemiological studies of SFV are often limited to captive populations. The southeastern Brazilian Atlantic Forest is home to both an endemic, endangered species, Leontopithecus rosalia, and an introduced species, Leontopithecus chrysomelas, to which no data on SFV exist. In this study, we assessed the molecular prevalence of SFV, their viral load, and their phylogenetic relationship in these two species of primates. Genomic DNA was extracted from 48 oral swab samples of L. chrysomelas and 102 of L. rosalia. Quantitative PCR (qPCR) was performed to diagnose SFV infection and quantify viral load. SFV prevalence was found to be 23% in L. chrysomelas and 33% in L. rosalia. No age-related differences in prevalence were observed; however, L. rosalia showed a higher mean viral load (3.27 log10/10⁶ cells) compared to L. chrysomelas (3.03 log10/10⁶ cells). The polymerase gene sequence (213 pb) of L. rosalia (SFVlro) was clustered within a distinct SFV lineage found in L. chrysomelas. The estimated origin of SFVlro dated back approximately 0.0836 million years ago. Our study provides the first molecular prevalence data for SFV in free-living Leontopithecus populations while offering insights into the complex evolutionary history of SFV in American primates. Full article

Human T-cell lymphotropic virus (HTLV), a retrovirus associated with severe conditions such as leukemia/lymphoma and myelopathy, exhibits variable global prevalence, with higher rates observed in regions such as northeastern Brazil and sub-Saharan Africa. While intrauterine transmission can occur via viral expression in placental tissue and contact with umbilical cord blood, the predominant route is vertical transmission through breastfeeding. Diagnostic testing, particularly serological screening with ELISA and confirmatory methods such as Western blot and PCR, is essential for early detection during pregnancy. The implementation of prenatal screening programs, as seen in Japan and Brazil, has proven effective in reducing vertical transmission by guiding interventions such as breastfeeding cessation in infected mothers. Beyond clinical implications, the psychosocial impact on affected pregnant women highlights the need for an interdisciplinary approach. Although the association between HTLV infection and adverse obstetric outcomes remains controversial, studies suggest increased risks of preterm birth, low birth weight, and other neonatal complications. Given the importance of early diagnosis and prevention, universal prenatal screening protocols represent a critical strategy to reduce viral transmission and its long-term consequences. Full article

Although ART leads to viral suppression, people living with HIV (PLWH) still face an increased risk of comorbidities, such as cancer. The HIV-1 Tat protein may contribute to the promotion of chronic inflammation, oxidative stress, and genomic instability. While the presence of anti-Tat antibodies has been associated with slower disease progression, their potential role in modulating DNA damage remains unclear. Assess the effect of anti-Tat antibodies on cytotoxic and DNA damage in PLWH. A cross-sectional study was conducted in 178 PLWH. Serum anti-Tat IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Cytotoxicity and DNA damage were assessed via serum 8-hydroxy-2′-deoxyguanosine (8-OHdG) and nuclear anomalies (Micronucleus cytome assay) in 2000 buccal cells. Statistical significance was considered at p < 0.05. Anti-Tat antibodies were found in 24.2% of participants. Positive individuals had lower CD4+ T cell counts (p = 0.045) and higher levels of pyknosis (p = 0.0001). No differences in 8-OHdG were found, but 8-OHdG correlated positively with CD4+ counts (rho = 0.334, p = 0.006). Pyknosis negatively correlated with CD4+ counts (rho = −0.272, p = 0.027). Anti-Tat antibodies may not prevent DNA damage but could be related to cytotoxic effects in PLWH. Full article

Improved antiretroviral therapy (ART) has significantly increased the life expectancy of people living with HIV (PLWH). At the same time, other complications like metabolic syndrome (MetS) are coming up as new challenges to handle. This review aims to explore the emerging evidence of gut microbiome and virome alterations in human immunodeficiency virus-1 (HIV-1) infection and associated metabolic disorders, such as type-2 diabetes (T2DM) and cardiovascular disease (CVD), with a focus on their interplay, contribution to immune dysfunction, and potential as therapeutic targets. We conducted a comprehensive review of the current literature on gut bacteriome and virome changes in HIV-1-infected individuals and those with metabolic comorbidities emphasizing their complex interplay and potential as biomarkers or therapeutic targets. HIV-1 infection disrupts gut microbial homeostasis, promoting bacterial translocation, systemic inflammation, and metabolic dysregulation. Similarly, metabolic disorders are marked by reduced beneficial short-chain fatty acid-producing bacteria and an increase in pro-inflammatory taxa. Alterations in the gut virome, particularly involving bacteriophages, may exacerbate bacterial dysbiosis and immune dysfunction. Conversely, some viral populations have been associated with immune restoration post-ART. These findings point toward a dynamic and bidirectional relationship between the gut virome, bacteriome, and host immunity. Targeted interventions such as microbiome modulation and fecal virome transplantation (FVT) offer promising avenues for restoring gut homeostasis and improving long-term outcomes in PLWH. Full article

T-cell receptors (TCRs) exhibit degeneracy, enabling individual TCRs to recognize multiple altered peptide ligands (APLs) derived from a single cognate antigen. This characteristic has been involved in the pathogenesis of autoimmune diseases through cross-reactivity between microbial and self-antigens. Cytotoxic T lymphocytes (CTLs), which recognize peptide–MHC class I complexes via TCRs, play a critical role in the immune response against viral infections. However, the extent to which TCR degeneracy within a population of virus-specific CTLs contributes to effective viral control remains poorly understood. In this study, we investigated the magnitude and functional relevance of TCR degeneracy in CTLs targeting an immunodominant epitope of human T-cell leukemia virus type 1 (HTLV-1) in patients with HTLV-1-associated myelopathy (HAM). Using peripheral blood mononuclear cells (PBMCs) from these patients, we quantified TCR degeneracy at the population level by comparing CTL responses to a panel of APLs with responses to the cognate epitope. Our findings demonstrated that increased TCR degeneracy, particularly at the primary TCR contact residue at position 5 of the antigen, was inversely correlated with HTLV-1 proviral load (p = 0.038, R = −0.40), despite similar functional avidity across patient-derived CTLs. Viral sequencing further revealed that CTLs with high TCR degeneracy exerted stronger selective pressure on the virus, as indicated by a higher frequency of nonsynonymous substitutions within the epitope-encoding region in patients with highly degenerate TCR repertoires. Moreover, TCR degeneracy was positively correlated with the recognition rate of epitope variants (p = 0.018, R = 0.76), suggesting that CTLs with high TCR degeneracy exhibited enhanced recognition of naturally occurring epitope variants compared to those with low TCR degeneracy. Taken together, these results suggest that virus-specific CTLs with high TCR degeneracy possess superior antiviral capacity, characterized by broadened epitope recognition and more effective suppression of HTLV-1 infection. To our knowledge, this is the first study to systematically quantify TCR degeneracy in HTLV-1-specific CTLs and evaluate its contribution to viral control in HAM patients. These findings establish TCR degeneracy as a critical determinant of antiviral efficacy and provide a novel immunological insight into the mechanisms of viral suppression in chronic HTLV-1 infection. Full article

Avian leukosis virus subgroup J (ALV-J), an α-retrovirus, mediates infection by binding to the host-specific receptor chNHE1 (chicken sodium–hydrogen exchanger type 1), leading to immunosuppression and tumorigenesis, which severely threatens the sustainable development of the poultry industry. Studies have shown that the tryptophan residue at position 38 (W38) of the chNHE1 protein is the critical site for ALV-J infection. In this study, we employed the CRISPR/Cas9 system to construct a lentiviral vector targeting the W38 site of chNHE1, transfected it into chicken primordial germ cells (PGCs), and validated its antiviral efficacy through ALV-J infection assays, successfully establishing an in vitro gene-editing system for chicken PGCs. The constructed dual lentiviral vector efficiently targeted the W38 site. PGCs isolated from 5.5- to 7-day-old chicken embryos were suitable for in vitro gene editing. Stable fluorescence expression was observed within 24–72 h post-transfection, confirming high transfection efficiency. ALV-J challenge tests demonstrated that no viral env gene expression was detected in transfected PGCs at 48 h or 72 h post-infection, while high env expression was observed in control groups. After 7 days of infection, p27 antigen ELISA tests were negative in transfected groups but positive in controls, indicating that W38-deleted PGCs exhibited strong resistance to ALV-J. This study successfully generated ALV-J-resistant gene-edited PGCs using CRISPR/Cas9 technology, providing a novel strategy for disease-resistant poultry breeding and advancing avian gene-editing applications. Full article

Human endogenous retroviruses (HERVs), as remnants of ancient exogenous retroviruses in the human genome, have received increased attention regarding their pathogenic effects caused by abnormal activation. In normal somatic cells, HERVs are tightly regulated by epigenetic mechanisms and are rarely expressed. In cancer cells, likely due to epigenetic dysregulation, HERVs become abnormally activated and are transcribed and expressed. The innate and adaptive immune responses triggered by HERV activation are closely associated with cancer initiation and progression. Melanoma, as a malignant tumor, often exhibits a poor prognosis in advanced-stage patients. HERVs have been found to be expressed in melanoma and linked to its malignant transformation. Here, we review the potential roles HERVs may play in melanoma development. As promising therapeutic targets for melanoma, research on HERVs could facilitate the development of novel treatment strategies. Full article

Lung cancer is a leading cause of cancer-related deaths globally, with current treatments having significant limitations, including drug resistance, metastasis, and tumor heterogeneity. This study investigated the anticancer potential of isalpinin, a flavonoid isolated from Paphiopedilum dianthum, against non-small cell lung cancer (NSCLC) cell lines A549, H23, and H460. Isalpinin significantly inhibited NSCLC cell viability in a dose- and time-dependent manner; H23 and H460 cells showed greater sensitivity (IC₅₀ a ~ 44 μM at 48 h) compared to A549 cells (IC₅₀ 82 μM). Isalpinin suppressed proliferation, migration, and anchorage-independent growth, particularly in H23/H460 cells. Mechanistically, it induced apoptosis via increased ROS production and Bcl-2 downregulation, particularly in H23 and H460 cells. In a molecular docking analysis, isalpinin was found to directly bind to the ATP-binding pocket of AKT1, as confirmed by reduced Akt/GSK3β phosphorylation. These results suggest that isalpinin showed a potent multi-target natural compound against NSCLC that disrupts the key hallmarks of malignancy and pro-survival signaling. However, its subtype-specific efficacy warrants further in vivo studies and an investigation of combinatorial therapeutic approaches to elucidate its clinical potential. Full article

AIDS-related malignant lymphomas (ARLs) are the lymphomas that develop in association with HIV infection. According to the introduction of combination antiretroviral therapy (cART), the life expectancy of People Living with HIV (PLWH) has markedly improved; however, approximately one-third of PLWH have passed away from the complications of malignancies, even in well-controlled PLWH. HIV itself is not tumorigenic, and most of these tumors are due to co-infection with oncogenic viruses. γ-herpes viruses (Epstein–Barr virus: EBV and Kaposi sarcoma-associated herpesvirus: KSHV) are the most significant risk factors for ARLs. Immunodeficiency, chronic inflammation, accelerated aging, and genetic instability caused by HIV infection, as well as HIV accessory molecules, are thought to promote lymphomagenesis. The prognosis of ARLs is comparable to that of non-HIV cases in the cART era. Intensive chemotherapy with autologous stem cell transplantation is also available for relapsed/refractory ARLs. Since the early stage of HIV infection has no symptoms, significant numbers of HIV-infected individuals have not noticed HIV infection until the onset of AIDS (so-called Ikinari AIDS). Since the ratio of these patients is more than 30% in Japan, hematologists should carefully consider the possibility of HIV infection in cases of lymphoma. Even in an era of cART, ARL remains a critical complication in PLWH, warranting continuous surveillance. Full article

Background/Objectives: Coronaviruses (CoVs) are a large family of respiratory viruses that cause respiratory illnesses ranging from mild colds to severe diseases such as severe acute respiratory syndrome and pandemics. The nasal cavity is a primary site for CoV entry and transmission. The study aimed to prepare a novel mucoadhesive emulgel specifically formulated with simple, safe, and cost-effective excipients to create a barrier on the nasal mucosa that impedes CoV infection. This formulation strategy was specifically designed to enable rapid and straightforward in vivo translation, addressing a critical gap in preventive measures against respiratory viruses. Methods: Three emulgels, containing macadamia oil, Carbopol and different percentages of hydroxypropyl methylcellulose (1, 1.2 and 1.5% (w/v), HPMC), were properly prepared and characterized for mucoadhesion, viscosity, and spreadability. The biological activity against SARS-CoV-2 was evaluated in vitro on infected epithelial cells. Results: The emulgel with 1.2% HPMC demonstrated optimal physicochemical properties (mucoadhesion: 342 ± 9 mN/cm²; viscosity: 1080 ± 83 cp; spreadability: 7.27 ± 0.06 cm) suitable for nasal application. Importantly, in vitro biological assays demonstrated that this emulgel significantly inhibits SARS-CoV-2 infection in epithelial cells, indicating an effective barrier to viral diffusion. Conclusions: By employing readily available, safe, and inexpensive excipients, this novel mucoadhesive emulgel offers a practical, scalable, and rapidly translatable nasal prophylactic approach to prevent early SARS-CoV-2 infection, addressing a critical unmet need in pandemic preparedness. Full article

Feline leishmaniasis (FeL), caused by Leishmania infantum, is increasingly reported in areas of endemic Mediterranean canine leishmaniasis (CanL), making it an emerging feline disease. This cross-sectional study investigated L. infantum seroprevalence and risk factors in 229 domestic cats from the Campania region of southern Italy, a CanL endemic area, between January 2023 and December 2024. Serum samples were tested for L. infantum antibodies (IFAT) and for FIV/FeLV. Seropositivity (IFAT titre ≥ 1:40) for FeL was detected in 12/229 (5.2%) of the cats tested. No statistically significant correlation was found between seropositivity for L. infantum and the variables considered. However, outdoor cats and FIV/FeLV-seropositive cats had higher prevalence rates: 10.6% and 7.4%, respectively. Of the 12 seropositive cats, 7 (58.3%) had an antibody titre of 1:40, 2 (16.6%) of 1:80 and 3 (25.0%) a titre of 1:160. Of the 12 cats positive for FeL, 2 (16.6%) were also positive for FIV. Our results confirm the exposure to L. infantum and the serological response in cats from southern Italy. The low prevalence could be due to owners using mosquito control products in the household that would also protect cats. Further investigation is essential to clarify risk factors and improve our understanding of the epidemiology of FeL in this endemic area. Full article

Glioblastoma multiforme (GBM) is a deadly disease known for its genetic heterogeneity. LTR12C is an endogenous retrovirus-derived regulator of pro-apoptotic genes and is normally silenced by epigenetic regulation. In this study, we found that the treatment of two glioblastoma cell lines, T98-G and U87-MG, with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors activated LTR12C expression. Combined treatment with these epigenetic drugs exerted a synergistic action on the LTR12C activation in both cell lines, while treatment with each drug as a single agent had a far weaker effect. A strong induction of the expression of the TP63 gene was seen in both cell lines, with the pro-apoptotic isoform GTA-p63 accounting for most of this increase. Coherently, downstream targets of p63, such as p21 and PUMA, were also induced by the combined treatment. Furthermore, we observed a significant reduction in the GBM cell growth and viability following the dual DNMT/HDAC inhibition. These findings reveal that the reactivation of LTR12C expression has the potential to modulate survival pathways in glioblastoma and provide information regarding possible epigenetic mechanisms that can be used to treat this deadly disease. Full article

Murine leukemia viruses (MuLVs) are retroviruses that cause various diseases in mice and have served as a model for retrovirus replication and pathogenesis. MuLVs are separated into infectious exogenous retroviruses (XRVs) and endogenous retroviruses (ERVs) that are remnants of ancient infectious XRVs. Detection of XRVs in the original host cells has some difficulties because of the high similarity in sequence between ERVs and XRVs and expression of some ERV genes. There are some techniques available for monitoring retroviral replication, but each comes with limitations in terms of labor intensity, detection range, cost, and phases after infection. This study developed a novel quantitative PCR (qPCR) method for assessing replication of Moloney MuLV (M-MuLV) in mouse cells. The method amplified the region in packaging signal and gag and distinguished exogenous M-MuLV from ERVs with mouse SC-1 cells. The qPCR system could quantify viral sequences in infected cells from 16 to 72 h post-infection, with a 3-log range of difference. This was compared with the traditional infectivity assay, focal immunofluorescence assay. In conclusion, the developed qPCR system provides a rapid, sensitive, and scalable alternative for quantifying M-MuLV infectivity, with potential for broader applications in MuLV research. Full article

This article summarizes the case of 30-year-old male diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and its longitudinal follow-up, which provided a secondary diagnosis of Multiple Sclerosis (MS) eight years later. The most impactful result was his response to rituximab treatment after the systematic failure of prior treatments. Although the expression of endogenous retroviral proteins has been associated with autoimmunity, the patient did not show increased expression of the toxic protein HERV (human endogenous retrovirus)-W ENV, a target of the ongoing clinical trials with temelimab in MS and long COVID-19 cases. However, genome-wide HERV transcriptome analysis by high density microarrays clearly revealed a distinct profile in the patient’s blood supportive of an altered immune system. Limitations of the study include sub-optimal frequency of magnetic resonance imaging to monitor lesion progression, and similarly for reassessment of HERV profiles after rituximab. Overall, the coincidence of HERV alterations and the impactful response to rituximab presents the possibility of additional, more specific, therapeutic targets encoded by other HERV elements yet to be discovered. Full article

Human T cell leukemia virus type 1 (HTLV 1) is an oncogenic retrovirus responsible for the development of adult T cell leukemia (ATL). The minus strand of HTLV-1 provirus encodes an oncoprotein named HTLV-1 bZIP factor (HBZ), which plays a pivotal role in viral replication and T cell proliferation. Of particular interest is the spliced HBZ isoform (sHBZ), which is predominantly expressed in ATL cells and localizes within the nucleolus, conferring immortalizing properties to T cells. Our previous study has shown that sHBZ colocalizes and associates with Nucleophosmin/B23, a nucleolar phosphoprotein with multiple functions. In this study, through an optimized nucleolar isolation method, we first confirmed sHBZ’s nucleolar localization via Western blotting in transfected HEK293T cells, chronically HTLV-1-infected T cell lines, and freshly infected HeLa cells. We further demonstrated that the sHBZ/B23 association predominantly occurs in the nucleolus by co-immunoprecipitation of cell fractions. Our study highlights the nucleolar localization of sHBZ and its possibly essential interaction with this nucleolar-residing protein, leading to cell immortalization. Full article