The online version contains supplementary material available at 10.1038/s41598-026-49324-2.

Virion infectivity factor (Vif), an accessory protein of HIV-1 (human immunodeficiency virus type 1), antagonizes host APOBEC3 protein (apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3) or A3 via proteasomal degradation, facilitating viral replication. HLA (Human leukocyte antigens) alleles, host restriction factors, and error-prone reverse transcription contribute to the global polymorphic dynamics of HIV, impacting effective vaccine design. Our computational analysis of over 50,000 HIV-1 M vif sequences from the Los Alamos National Laboratory (LANL) database (1998-2021) revealed positive selection pressure on the vif gene (nonsynonymous to synonymous ratio, dn/ds=1.58) and an average entropy score of 0.372 in protein level. Interestingly, over the years (1998-2021), a decreasing trend of dn/ds (1.68 to 1.47) and an increasing trend of entropy (0.309 to 0.399) was observed. The predicted mutational frequency against Vif consensus sequence decreased over time (slope = -0.00024, p < 0.0001). Sequence conservation was observed in Vif functional motifs F1, F2, F3, G, BC box, and CBF β binding region, while variability was observed mainly in N- and C- terminal and Zinc finger region, which were dominantly under immune pressure by host HLA-I-restricted CD8+ T cell. Computational analysis of ∆∆G^stability through protein stability prediction tools suggested that missense mutation may affect Vif stability, especially in the Vif-A3 binding interface. Notably, mutations R17K and Y44F in F1 and G box were predicted to destabilize the Vif-A3 binding interface by altering bond formations with adjacent amino acids. Therefore, our analysis demonstrates Vif adaptation with host physiology by maintaining sequence conservation, especially in A3 interacting functional motifs, highlighting important therapeutic candidate regions of Vif against HIV-1 infections.

HIV-1 escapes by acquiring mutations that differentially influence the course of infection. Unlike HIV-1 structural and enzymatic proteins, it remains elusive what extent the host immune-mediated selection pressure influences the variability of the accessory (Vif, Vpu, Vpr, and Nef) and regulatory (Tat and Rev) proteins. To address this, we analyzed the viral sequences encoding accessory and regulatory proteins from 446 human leukocyte antigen (HLA)-typed, chronically HIV-1 subtype B-infected, and treatment-naive individuals in Japan. We observed that Vpu and Vpr were the most and least polymorphic proteins with the average Shannon entropy scores of 0.63 and 0.38, respectively. Phylogenetically corrected methods identified a total of 161 HLA-associated polymorphisms; whereby Nef and Vpu had the highest (26.6%) and lowest (1.2%) proportion of amino acid sites associated with HLA-class I alleles, respectively. These results add further insight on the role of HLA-mediated selection pressure on HIV-1 sequence polymorphisms of HIV-1 accessory and regulatory proteins.

Background: Betel quid (BQ) chewing is a common habit and a means of social interaction among the northeastern peoples of Bangladesh. Though this habit integrating in their daily life without knowing its toxic effect. Areca nut, which is one of the main components of BQ and may responsible for this addiction. Here, we assess to see how BQ chewing habit influence hyperglycemia among diabetic patients with respect to their lifestyle. Methodology: Random blood sugar (RBS) test was evaluated from a total of 961 diabetic patients. Behavioral data associated with their daily lifestyle were collected from August 2018 to February 2019 from Sylhet Diabetic Hospital, Bangladesh. Student’s t-test, ANOVA and Fisher’s exact test were used to assess the RBS status between BQ chewer and non-chewer patients. Results: Higher RBS was found in BQ chewer patients than non-chewer (mean ± SEM, 263.3 ± 4.768 vs. 251.0 ± 5.915mg/dl). Interestingly, it is significantly higher in raw areca nut user than dry nut (mean ± SEM, 278.0 ± 8.790 vs. 252.1 ± 6.835 mg/dl) only from BQ chewer group, suggesting that the habit of chewing raw nut may contribute to more hyperglycemic effect among diabetic patients. BQ habit enhances higher RBS level among smoker, non-smoker and patient’s having walking habit. In addition, BQ habit significantly influence to have high RBS in patients with family history with diabetes. Lack of awareness being diabetes have also been observed significantly in BQ chewer patients, while a higher level of RBS was seen in BQ group, who work in different sectors with sitting activities. Conclusions: Diabetic patients who chew betel quid are more prone to keep higher hyperglycemic. Utmost attention should be taken to discourage the use of BQ for proper management of diabetes control.