Reactive oxygen species (ROS) are widely regarded as signaling molecules and play essential roles in various cellular processes, but when present in excess, they can lead to oxidative stress (OS). Growing evidence suggests that the OS plays a critical role in the pathogenesis of HIV infection and is associated with several comorbidities in HIV-infected individuals. ROS, generated both naturally during mitochondrial oxidative metabolism and as a response to various cellular processes, can trigger host antiviral responses but can also promote viral replication. While the multifaceted roles of ROS in HIV pathophysiology clearly need more investigation, this review paper unravels the mechanisms of OS generation in the context of HIV infections, offering insights into HIV viral protein-mediated and antiretroviral therapy-generated OS. Though the viral protein Tat is significantly attributed to the endogenous cellular increase in ROS post HIV infection, this paper sums up the contribution of other viral proteins in HIV-mediated elicitation of ROS. Given the investigations recognizing the significant role of ROS in the onset and progression of diverse pathologies, the paper also explores the critical function of ROS in the mediation of an of array of pathologies associated with HIV infection and retroviral therapy. HIV patients are observed with disruption to the antioxidant defense system, the antioxidant therapy is gaining focus as a potential therapeutic intervention and is well discussed. While ROS play a significant role in the HIV scenario, further exploratory studies are imperative to identifying alternative therapeutic strategies that could mitigate the toxicities and pathologies associated with ART-induced OS.

HPV, or Human Papilloma Virus, has been the primary causative agent of genital warts and cervical cancer worldwide. It is a sexually transmitted infection mainly affecting women of reproductive age group, also infecting men and high-risk group individuals globally, resulting in high mortality. In recent years, HPV has also been found to be the major culprit behind anogenital cancers in both gender and oropharyngeal and colorectal cancers. Few studies have reported the incidence of HPV in breast cancers as well. For a few decades, the burden of HPV-associated malignancies has been increasing at an alarming rate due to a lack of adequate awareness, famine vaccine coverage and hesitancy. The effectiveness of currently available vaccines has been limited to prophylactic efficacy and does not prevent malignancies associated with post-exposure persistent infection. This review focuses on the current burden of HPV-associated malignancies, their causes and strategies to combat the growing prevalence of the cancers. With the advent of new technologies associated with treatment pertaining to therapeutic interventions and employing effective vaccine coverage, the burden of this disease may be reduced in the population.

Antiretroviral therapy is the only treatment option for HIV-infected patients; however, it has certain drawbacks in terms of developing multiple toxic side effects. Thus, there is a continuous need to explore safe and efficacious anti-retroviral agents. Carica papaya Linn and Psidium guajava are known for their various biological activities. In this study, we characterized the bioactive fractions of methanolic leaves extract from both plants using the High-resolution electrospray ionization mass spectrometry (HR-ESI–MS) technique, followed by the investigation of their potential as anti-HIV-1 and antioxidant agents through in vitro mechanistic assays. The anti-HIV-1 activity was examined in TZM-bl cells through luciferase gene assay against two different clades of HIV-1 strains, whereas the intracellular ROS generation was analyzed by Fluorescence-Activated Cell Sorting. Additionally, the mechanisms of action of these phyto-extracts were determined through the Time-of-addition assay. The characterization of Carica papaya Linn and Psidium guajava leaves extract through HR-ESI–MS fragmentation showed high enrichment of various alkaloids, glycosides, lipids, phenolic compounds, terpenes, and fatty acids like bioactive constituents. Both the phyto-extracts were found to be less toxic and exhibited potent antiviral activity against HIV-1 strains. Furthermore, the phyto-extracts also showed a decreased intracellular ROS in HIV-1 infected cells due to their high antioxidant potential. Overall, our study suggests the anti-HIV-1 potential of Carica papaya Linn and Psidium guajava leaves extract due to the synergistic action of multiple bioactive constituents.

Background: Several anti-retroviral drugs are available against Human immunodeficiency virus type-1, but have multiple adverse side effects. Hence, there is an incessant compulsion for effectual anti-retroviral agents with minimal or no intricacy. Traditionally, natural products have been the most successful source for the development of new medications. Withania somnifera, also known as Ashwagandha, is the utmost treasured medicinal plant used in Ayurveda, which holds the potential to give adaptogenic, immunomodulatory, and antiviral effects. However, its effect on HIV-1 replication at the cellular level has never been explored. Herein, we focused on the anti-HIV-1 activity and the probable mechanism of action of hydroalcoholic and aqueous extracts of Withania somnifera roots and its phytomolecules. Methods: The cytotoxicity of the extracts was determined through MTT assay, while the in vitro anti-HIV-1 activity was assessed in TZM-bl cells against the HIV-1 strains of X4 and R5 subtypes. Results were confirmed in peripheral blood mononuclear cells, using the HIV-1 p24 antigen assay. Additionally, the mechanism of action was determined through the Time of Addition assay, which was further validated through the series of enzymatic assays, i.e. HIV-1 Integrase, Reverse transcriptase, and Protease assays. To explore the role of the identified active metabolites of Withania somnifera in antiretroviral activity, molecular docking analyses were performed against these key HIV-1 replication enzymes. Results: The hydroalcoholic and aqueous extracts of Withania somnifera roots were found to be safer at the sub-cytotoxic concentrations and exhibited their ability to inhibit replication of two primary isolates of HIV-1 through cell-associated and cell-free assays, in dose-dependent kinetics. Several active phytomolecules found in Withania somnifera successfully established hydrogens bonds in the active binding pocket site residues responsible for the catalytic activity of HIV replication and therefore, signifying their role in the attenuation of HIV-1 infection as implied through the in silico molecular docking studies. Conclusions: Our research identified both the hydroalcoholic and aqueous extracts of Withania somnifera roots as potent inhibitors of HIV-1 infection. The in silico analyses also indicated the key components of Withania somnifera with the highest binding affinity against the HIV-1 Integrase by 12-Deoxywithastramonolide and 27-Hydroxywithanone, HIV-1 Protease by Ashwagandhanolide and Withacoagin, and HIV-1 Reverse transcriptase by Ashwagandhanolide and Withanolide B, thereby showing possible mechanisms of HIV-1 extenuation. Overall, this study classified the role of Withania somnifera extracts and their active compounds as potential agents against HIV-1 infection.

Epstein–Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), which are the only members of the gamma(γ) herpesviruses, are oncogenic viruses that significantly contribute to the development of various human cancers, such as Burkitt’s lymphoma, nasopharyngeal carcinoma, Hodgkin’s lymphoma, Kaposi’s sarcoma, and primary effusion lymphoma. Oncogenesis triggered by γ-herpesviruses involves complex interactions between viral genetics, host cellular mechanisms, and immune evasion strategies. At the genetic level, crucial viral oncogenes participate in the disruption of cell signaling, leading to uncontrolled proliferation and inhibition of apoptosis. These viral proteins can modulate several cellular pathways, including the NF-κB and JAK/STAT pathways, which play essential roles in cell survival and inflammation. Epigenetic modifications further contribute to EBV- and KSHV-mediated cancerogenesis. Both EBV and KSHV manipulate host cell DNA methylation, histone modification, and chromatin remodeling, the interplay of which contribute to the elevation of oncogene expression and the silencing of the tumor suppressor genes. Immune factors also play a pivotal role in the development of cancer. The γ-herpesviruses have evolved intricate immune evasion strategies, including the manipulation of the major histocompatibility complex (MHC) and the release of cytokines, allowing infected cells to evade immune detection and destruction. In addition, a compromised immune system, such as in HIV/AIDS patients, significantly increases the risk of cancers associated with EBV and KSHV. This review aims to provide a comprehensive overview of the genetic, epigenetic, and immune mechanisms by which γ-herpesviruses drive cancerogenesis, highlighting key molecular pathways and potential therapeutic targets.

Background: The interaction between HIV-1 and host immune cells, particularly macrophages, is crucial in understanding viral persistence and pathogenesis. This study aims to explore the impact of HIV-1 infection on macrophage microRNA (miRNA) expression profiles using a systems biology approach to uncover the potential role of miRNAs in modulating macrophage functionality and identify key miRNA targets that may serve as therapeutic avenues. Methods: PMA-differentiated THP-1 cells were used to model macrophage infection with HIV-1. A custom miRNA microarray was performed to identify dysregulated miRNAs following infection. miRTarBase was utilized for miRNA target identification, revealing gene targets associated with the dysregulated miRNAs. A protein-protein interaction (PPI) map of miRNA targets and their first interactors was constructed, with key nodes identified based on a calculated disease score, which considered degree, betweenness centrality, average shortest path length, and clustering coefficient. Gene Ontology molecular function analysis was also conducted on the identified targets. Results: The miRNA microarray identified 23 dysregulated miRNAs in HIV-1-infected macrophages, with 8 upregulated and 15 downregulated. Among these, the top 10 dysregulated miRNAs targeted over 2000 unique genes. PPI analysis revealed key nodes in the upregulated miRNA network, including APP , MYC , ESR2 , RAF1 , and HIST1H4A , while ZRANB1 , HSPA8 , TGOLN2 , HSPA5 , and BRD4 were prominent in the downregulated miRNA network. Notably, KRAS , CUL3 , TP53 , ESR1 , and PARP1 were influenced by both upregulated and downregulated miRNAs. Gene Ontology analysis indicated that the targeted genes were involved in processes such as protein and RNA binding, ATPase activity, and ribosomal function. Conclusions: HIV-1 infection induces significant dysregulation of miRNAs in macrophages, impacting a wide array of gene targets and molecular functions. These findings suggest that miRNA-mediated regulation may play a crucial role in HIV-1 pathogenesis within macrophages and present potential targets for miRNA-based therapeutic strategies.