锌,一种必需的微量元素,可作为多种细胞和病毒蛋白的辅因子,在HIV-1感染的动态中起着核心作用。在病毒蛋白中,核衣壳NCp7,其中包含两个锌指基序,大量存在的病毒颗粒,在包被HIV-1基因组RNA中起着至关重要的作用,从而在病毒体中浓缩锌。在这项研究中,我们调查了HIV-1病毒产生是否影响细胞锌稳态,以及生长培养基之间是否发生同位素分馏,生产细胞,和病毒颗粒。我们发现HIV-1在新产生的颗粒中捕获了相当大比例的细胞锌。此外,随着细胞的生长,它们从培养基中积累了较轻的锌同位素,导致介质中的较重同位素浓度,病毒表现出与生产细胞相似的同位素分级。此外,我们在HEK293T细胞中产生了富含5种锌同位素的HIV-1颗粒,以评估对病毒结构和感染性的潜在影响.由于在各种条件下产生的HIV-1颗粒之间没有观察到强烈的差异,我们已经证明,富集同位素可以在未来的研究中准确地用于追踪被HIV-1颗粒感染的细胞中锌的命运.了解HIV-1病毒颗粒吸收锌的潜在机制,有可能为开发旨在解决病毒生命周期这一特定方面的未来治疗方法提供见解。
Zinc, an essential trace element that serves as a cofactor for numerous cellular and viral proteins, plays a central role in the dynamics of HIV-1 infection. Among the viral proteins, the nucleocapsid NCp7, which contains two zinc finger motifs, is abundantly present viral particles and plays a crucial role in coating HIV-1 genomic RNA, thus concentrating zinc within virions. In this
study, we investigated whether HIV-1 virus production impacts cellular zinc homeostasis and whether isotopic fractionation occurs between the growth medium, the producing cells, and the viral particles. We found that HIV-1 captures a significant proportion of cellular zinc in the neo-produced particles. Furthermore, as cells grow, they accumulate lighter zinc
isotopes from the medium, resulting in a concentration of heavier
isotopes in the media, and the viruses exhibit a similar isotopic fractionation to the producing cells. Moreover, we generated HIV-1 particles in HEK293T cells enriched with each of the five zinc
isotopes to assess the potential effects on the structure and infectivity of the viruses. As no strong difference was observed between the HIV-1 particles produced in the various conditions, we have demonstrated that enriched
isotopes can be accurately used in future studies to trace the fate of zinc in cells infected by HIV-1 particles. Comprehending the mechanisms underlying zinc absorption by HIV-1 viral particles offers the potential to provide insights for developing future treatments aimed at addressing this specific facet of the virus\'s life cycle.