Moyes D L, Islam A, Kohli A, Naglik J R
Mucosal & Salivary Biology Division, King's College London Dental Institute, King's College London, London, UK.
Public Health England, London, UK.
Oral Dis. 2016 Apr;22 Suppl 1:66-72. doi: 10.1111/odi.12410. Epub 2016 Feb 16.
As the AIDS pandemic has continued, our understanding of the events that occur during the entry and infection of conventional, susceptible cells has increased dramatically, leading to the development of control therapies for HIV-infected individuals. However, an ongoing hole in our understanding is how HIV crosses the mucosal barriers to gain access to permissive cells, despite how important this information would be in developing successful vaccines and other preventative measures such as topical anti-HIV microbicides. In particular, our knowledge of the role that epithelial cells of the mucosal surfaces play in infection - both during early phases and throughout the life of an infected individual, is currently hazy at best. However, several studies in recent years suggest that HIV can bind to and traverse these mucosal epithelial cells, providing a reservoir of infection that can subsequently infect underlying permissive cells. Despite this interaction with epithelial cells, evidence suggests HIV-1 does not productively infect these cells, although they are capable of transferring surface-bound and transcytosed virus to other, permissive cells. Further, there appear to be key differences between adult and infant epithelial cells in the degree to which HIV can transcytose and infect the epithelium. Thus, it is clear that, whilst not primary targets for infection and virus replication, epithelial cells play an important role in the infection cycle and improving our understanding of their interactions with HIV could potentially provide key insights necessary to develop effective preventative therapies.
随着艾滋病大流行的持续,我们对传统易感细胞进入和感染过程中所发生事件的理解有了显著提高,这促使了针对HIV感染者的控制疗法的发展。然而,我们目前仍存在一个认知缺口,即尽管了解HIV如何穿过黏膜屏障以接触到易感细胞对于开发成功的疫苗和其他预防措施(如局部抗HIV杀微生物剂)至关重要,但我们对此仍知之甚少。特别是,我们对黏膜表面上皮细胞在感染过程中所起的作用(无论是在早期阶段还是在感染者的整个生命周期内)的了解目前充其量也只是模糊不清。然而,近年来的几项研究表明,HIV能够结合并穿过这些黏膜上皮细胞,形成一个感染库,随后可感染其下方的易感细胞。尽管存在与上皮细胞的这种相互作用,但有证据表明HIV-1并不会有效感染这些细胞,尽管它们能够将表面结合和跨细胞转运的病毒传递给其他易感细胞。此外,成人和婴儿的上皮细胞在HIV跨细胞转运和感染上皮细胞的程度上似乎存在关键差异。因此,很明显,虽然上皮细胞不是感染和病毒复制的主要靶标,但它们在感染周期中起着重要作用,增进我们对它们与HIV相互作用的理解可能会为开发有效的预防疗法提供必要的关键见解。