Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
PLoS One. 2011;6(8):e23542. doi: 10.1371/journal.pone.0023542. Epub 2011 Aug 11.
Interaction with the complement system is an underappreciated aspect of HIV-1 infection; even in primary infection, complement fragments are found on virions with potential to affect the interplay between the virus and dendritic cells (DC). Since opsonization may affect the efficiency of uptake and the type of receptors utilized, we compared the interactions of DC with free HIV-1 (F-HIV) and complement opsonized HIV-1 (C-HIV). We demonstrate that C-HIV significantly enhanced the uptake by immature DC (IDC) and mature DC (MDC) and that the internalization rate was dependent on both opsonization of the virus and DC maturation state. Increased DC uptake of C-HIV was not due to opsonization related increased binding of virus to the surface of DC but rather increased internalization of C-HIV despite utilizing a similar repertoire of receptors as F-HIV. Both F-HIV and C-HIV interacted with C-type lectins, integrins, and CD4 and blocking these receptor families prevented HIV-1 from binding to DC at 4°C. Blocking integrins significantly reduced the binding and uptake of F-HIV and C-HIV implicating the involvement of several integrins such as β1-integrin, CR3, LFA-1, and α4β7. Distinctive for C-HIV was usage of β1-integrin and for F-HIV, usage of β7-integrin, whereas both F-HIV and C-HIV utilized both integrin chains of CR3. We have in this study identified the receptor types used by both F-HIV and C-HIV to bind to DC. Noteworthy, C-HIV was internalized more efficiently by DC than F-HIV, probably via receptor mediated endocytosis, which may entail different intracellular processing of the virus leading to both elevated infection and altered activation of HIV specific immune responses.
HIV-1 感染过程中，补体系统的相互作用是一个尚未被充分认识的方面；即使在初次感染时，病毒颗粒上也存在补体片段，有可能影响病毒与树突状细胞（DC）之间的相互作用。由于调理作用可能会影响病毒的摄取效率和所利用的受体类型，我们比较了 DC 与游离 HIV-1（F-HIV）和补体调理的 HIV-1（C-HIV）的相互作用。我们证明，C-HIV 可显著增强未成熟 DC（IDC）和成熟 DC（MDC）的摄取，内化率既依赖于病毒的调理，也依赖于 DC 的成熟状态。C-HIV 增加了 DC 的摄取，这不是由于调理作用导致病毒与 DC 表面的结合增加，而是由于 C-HIV 的内化增加，尽管它利用了与 F-HIV 相似的受体谱。F-HIV 和 C-HIV 均与 C 型凝集素、整合素和 CD4 相互作用，阻断这些受体家族可防止 HIV-1 在 4°C 时与 DC 结合。阻断整合素可显著降低 F-HIV 和 C-HIV 的结合和摄取，表明涉及几种整合素，如β1-整合素、CR3、LFA-1 和α4β7。C-HIV 的特点是使用β1-整合素，而 F-HIV 则使用β7-整合素，而 F-HIV 和 C-HIV 均利用了 CR3 的两条整合素链。在这项研究中，我们确定了 F-HIV 和 C-HIV 结合 DC 时所使用的受体类型。值得注意的是，C-HIV 比 F-HIV 更有效地被 DC 内化，可能通过受体介导的内吞作用，这可能需要对病毒进行不同的细胞内处理，从而导致感染增加和 HIV 特异性免疫反应的激活改变。
