HIV-1 transmission and spread involves significant host-virus interaction. Possible targets for obstacle of HIV-1 lie at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and leads their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. For the viral infectivity and pathogenicity, HIV-1 Nef facilitates immune evasion through protein-protein interactions within host cell. HIV-1 Nef is significant for viral infectivity and pathogenicity. It enhances HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study, HIV-1 Nef forms with specific mutations, revealing sequence variability, were studied for their effects in human SupT1 T cell line and (THP-1) monocyte-macrophage cell line. Proteins being downregulated by Nef in SupT1 were further observed in THP-1, and interestingly two host proteins' (ENO-1 and VDAC1) expression was found to be cell lineage specific, being stimulatory in macrophages/monocytes and inhibitory in T cells. Cell migration, invasion and ADP release studies were employed to determine the biological function affected by Nef-mediated regulation of these two host proteins. ENO1-regulated function: cell invasion was enhanced in THP-1 cells, but was inhibited in SupT1 cells by Nef RP01. In addition, the modulation of proteins and cell invasion remained unaffected by a Nef RP14. These results indicated that regulation of host protein expression and invasive property of host cells by Nef was sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the CAWLEAQ-regulating sequence of Nef. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers were particularly investigated by the peptide. The peptide led to reversal of differential expressions of ENO1 in both SupT1 and THP-1 and inhibition of enhanced invasiveness in THP-1 cells. Further AP-1 was identified as a factor involved in this Nef-mediated regulation of host proteins. Together these findings suggest a possible mechanism of host invasion by HIV-1 through the CAWLEAQ motif of Nef-mediated regulation of ENO1 and identify a potential therapeutic target for HIV-1 entry at mucosal barriers.Keywords: AP1; Cell invasion; HIV-1 Nef; Host–virus interaction; Nef variants.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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