Human immunodeficiency virus type 1 (HIV-1) causes progressive immune dysfunction and, if untreated, can lead to acquired immunodeficiency syndrome (AIDS). Although combination antiretroviral therapy (cART) effectively suppresses viral replication and has substantially improved outcomes for people living with HIV (PLWH), it does not eradicate persistent viral reservoirs and requires lifelong treatment. Consequently, research continues to explore immunotherapeutic strategies that may enhance antiviral immunity and contribute to HIV-1 prevention, remission, or eradication. Natural killer (NK) cells have emerged as promising candidates in HIV-1 research because of their innate cytotoxic activity, functional diversity, adaptability, and expression of receptors involved in antiviral responses, including the NKG2 receptor family and CD16. Several NK cell-based immunotherapeutic approaches are currently under investigation, with varying mechanisms and potential applications. This review examines the current landscape of NK cell immunotherapies for HIV-1 and highlights approaches demonstrating the greatest potential relevance to HIV-1 vaccine development, including a proposed conceptual model. A PubMed literature search was conducted using terms including “NK cells,” “HIV,” “HIV vaccine,” and “NK immunotherapies.” Current evidence suggests that several NK cell-based strategies demonstrate promising antiviral activity and supports continued investigation of NK cell immunotherapies for HIV-1 treatment and prevention, particularly approaches that may inform the development of an effective HIV-1 vaccine.
Chronic hepatitis B virus (HBV) infection is a significant cause of progressive liver disease and cirrhosis, often accompanied by hematological complications, including anemia. Evidence increasingly indicates that eryptosis—the programmed death of erythrocytes—may play a role in disrupting red blood cell balance in chronic liver conditions. Eryptosis is characterized by phosphatidylserine externalization, intracellular calcium accumulation, oxidative stress, and ceramide-dependent signaling pathways. Entecavir, a highly effective antiviral medication, is used to consistently suppress HBV replication in patients with chronic hepatitis B and HBV-related cirrhosis. Entecavir-induced viral suppression is associated with improved hepatic function, biochemical markers, and clinical outcomes. However, direct evidence on the effects of HBV suppression on red blood cell survival, eryptosis, and anemia is lacking. In this review, we summarize current knowledge of eryptosis in HBV-related liver cirrhosis, focusing on its molecular mechanisms, biomarkers, and potential role in anemia. We also review the documented effects of entecavir on virological, biochemical, and hematologic parameters, and discuss possible indirect links between viral suppression, restored hepatic function, and erythrocyte homeostasis. Direct evidence linking entecavir therapy to changes in eryptosis remains scarce, underscoring the need for prospective clinical and experimental studies.
Retrotransposons (RTEs), which comprise nearly half of the mammalian genome, are silenced in adult somatic tissues but can be reactivated by physiological stimuli and in diseases. Here, we focus on adult regenerative tissues, particularly blood and skin, where RTE regulation requires a delicate balance between maintaining faithful silencing and harnessing physiological RTE activity to support stem cell maturation, stress responses, and interactions with tissue niches, and excessive reactivation can lead to stem cell exhaustion and tissue dysfunction. We summarize studies of RE-derived nucleic acids that, when aberrantly activated, engage innate immune sensors and trigger antiviral responses, linking RTE activity to inflammatory disorders. We further review experimental evidence in cancer, where RTE reactivation creates a battleground between antiviral defense and immune evasion, and emerging evidence suggesting that RTEs may mediate communication between peripheral tissues and the hematopoietic system. Finally, while experimental evidence is promising, clinical studies targeting RTE activity have produced mixed outcomes. We therefore conclude by highlighting the need for deeper mechanistic investigations.
Dengue virus (DENV) is a mosquito-borne, positive sense, single-stranded RNA virus that includes four serotypes (DENV1-4) that are further divided into distinct genotypes within a serotype. DENV causes approximately 100 million human infections each year. DENV virions encode a capisd surrounded by a lipid bilayer that encodes two glycoproteins, E and prM. During virion maturation, the premembrane protein (prM) is cleaved to form a mature virion, which includes partially mature and fully mature particles. The maturity state of the DENV virion affects both the infectivity of DENVs and the ability of antibodies to neutralize the virus. The prM glycoprotein is glycosylated and highly conserved across all DENVs. In particular, the N-linked glycosylation site at position 69 is present in over 99% of DENV genomes. In this manuscript, we investigated the importance of the N69 glycosylation site by generating both DENV2 and DENV4 loss-of-function viruses. These N69 glycosylation knockout viruses were generated by introducing a single amino acid mutation at site 69. Neither mutant virus had detectable titers despite multiple passages in vitro. To further investigate the importance of the glycosylation site, we generated another variation in which the N-linked glycosylation site was repositioned to a site proximal to residue 69. One of these proximal-glycosylation mutants showed viral replication at levels that approached wild-type (WT) DENV strains. Overall, this study demonstrated the importance of retaining an N-linked glycan on the prM protein at position 69 for DENV infectivity of mosquito cells and that inserting a glycosylation site in close proximity to position 69 may restore infectivity in some DENV4 strains.
Transposable elements (TEs) have long been viewed as selfish genetic elements whose mobilization threatens genome integrity. However, increasing evidence from development, disease, and comparative genomics has revealed that TE-derived DNA, RNA, and proteins can be retained, repurposed, and repeatedly co-opted by host genomes. A central challenge is that TE function is highly context-dependent, where the same families that are silenced in most somatic cells can become active in early development, cancer, neural differentiation, immune activation, or experimentally sensitized chromatin states. Here, we review recent discoveries showing how TE-derived sequences contribute to gene regulation, three-dimensional genome organization, neurodevelopment, myelination, immunity, and disease-associated transcriptional programs. We emphasize that development and disease can expose shared regulatory capacities of TEs, and we discuss how long-read sequencing, TE-aware transcriptomics, chromatin profiling, and locus-specific perturbation are changing how the field interprets the TE record. In addition to asking whether TEs are selfish or beneficial, we argue that the field must ask when, where, and by what mechanism TE-derived sequences become functional.
