Lambert Gregory S, Siedlecki Christopher A, Parent Leslie J
Department of Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Department of Surgery, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Int J Mol Sci. 2025 Jun 13;26(12):5679. doi: 10.3390/ijms26125679.
The continued effective control of retroviral infections will no doubt require the development of new clinical interventions targeting underexploited areas of retroviral biology such as genome selection and virion assembly. In our previous work, we demonstrated that both the Gag-psi (Ψ) interaction and genomic RNA (gRNA) dimerization each uniquely contribute to the formation, morphology, and stability of Rous sarcoma virus (RSV) Gag-viral RNA (vRNA) biomolecular condensates (BMCs). The present work builds upon those observations, utilizing atomic force microscopy (AFM) and fluorescence correlation spectroscopy (FCS) to elucidate the nanoscale morphology, resistance to mechanical deformation, and constituent diffusivity of RSV Gag-vRNA BMCs. These approaches revealed a novel role for gRNA dimerization in nanoscale condensate architecture and mechanical stability that aids in our understanding of why gRNA dimerization is critical for efficient packaging of the retroviral genome. Further biophysical characterization of RSV Gag-gRNA BMCs therefore possesses great potential to reveal novel avenues for therapeutic intervention.
持续有效地控制逆转录病毒感染无疑需要开发针对逆转录病毒生物学中未充分利用领域（如基因组选择和病毒体组装）的新临床干预措施。在我们之前的工作中，我们证明了Gag-ψ（Ψ）相互作用和基因组RNA（gRNA）二聚化各自独特地促进了劳斯肉瘤病毒（RSV）Gag-病毒RNA（vRNA）生物分子凝聚物（BMCs）的形成、形态和稳定性。目前的工作基于这些观察结果，利用原子力显微镜（AFM）和荧光相关光谱（FCS）来阐明RSV Gag-vRNA BMCs的纳米级形态、抗机械变形能力和组分扩散率。这些方法揭示了gRNA二聚化在纳米级凝聚物结构和机械稳定性中的新作用，这有助于我们理解为什么gRNA二聚化对于逆转录病毒基因组的有效包装至关重要。因此，对RSV Gag-gRNA BMCs的进一步生物物理表征具有揭示新治疗干预途径的巨大潜力。
