高危人乳头瘤病毒（HR-HPV）持续感染艾滋病病毒-1（HIV-1）的女性。 HPV-16在接受联合抗逆转录病毒疗法（cART）的HIV-1阳性女性中逃逸免疫监视。 HIV-1 Tat和HPV E6 / E7蛋白利用Notch信号。Notch-1是一个发育上保守的蛋白质，从出生到死亡都影响细胞命运。 Notch-1及其下游靶点Hes-1和Hey-1有助于浸润性和侵袭性癌症。宫颈癌细胞利用Notch-1并超表达CXCR4，这是HIV-1的共受体。积累的证据表明，HIV-1影响现有HPV感染的细胞周期进程。此外，Tat通过结合Notch-1受体进行激活并影响细胞增殖。致癌病毒可能干扰或汇聚在一起以促进肿瘤生长。目前还没有探究HIV-1 / HPV-16 +共感染情况下Notch-1信号传导的分子对话。本研究采用转染有质粒（pLEGFPN1编码HIV-1 Tat和pNL4-3编码HIV-1 [完整HIV-1基因组]）的细胞系（HPV-ve C33A和HPV-16 + CaSki）进行体外研究。 HIV-1 Tat和HIV-1抑制Notch-1表达，对EGFR有不同的影响。 Notch-1抑制令Cyclin D表达失效，p21诱导并增加CaSki细胞中的G2-M细胞群。相反，HIV-1感染通过Notch-1下游基因Hes-1-EGFR和Cyclin D相互作用令p21表达关闭以进行G2-M停滞，DDR反应和癌症进展。本研究为未来的研究和干预奠定了基础，因此是必需的。我们的结果首次描述了HIV-1 Tat癌症由于Notch-1和EGFR信号之间的相互作用而具有侵袭性。在器官癌治疗中使用的Notch-1抑制剂DAPT可能有助于拯救HIV-1引起的癌症。图示了HIV如何与HPV-16相互作用以诱导Notch 1抑制来促进癌症进展（使用BioRender.com创建）。在线版本包含可在10.1007/s13337-023-00809-y获得的补充材料。©作者，在印度病毒学会的独家许可下，Springer Nature或其许可方（例如协会或其他伙伴）在出版协议中独家拥有本文章的专有权利；作者自行归档接受的手稿版本仅受该出版协议和适用法律的约束。

High Risk Human Papilloma Viruses (HR-HPV) persistently infect women with Human Immunodeficiency Virus-1 (HIV-1). HPV-16 escapes immune surveillance in HIV-1 positive women receiving combined antiretroviral therapy (cART). HIV-1 Tat and HPV E6/E7 proteins exploit Notch signaling. Notch-1, a developmentally conserved protein, influences cell fate from birth to death. Notch-1 and its downstream targets, Hes-1 and Hey-1 contribute to invasive and aggressive cancers. Cervical cancer cells utilize Notch-1 and hyper-express CXCR4, a co-receptor of HIV-1. Accumulating evidence shows that HIV-1 affects cell cycle progression in pre-existing HPV infection. Additionally, Tat binds Notch-1 receptor for activation and influences cell proliferation. Oncogenic viruses may interfere or converge together to favor tumor growth. The molecular dialogue during HIV-1/HPV-16+ co-infections in the context of Notch-1 signaling has not been explored thus far. This in vitro study was designed with cell lines (HPV-ve C33A and HPV-16+ CaSki) which were transfected with plasmids (pLEGFPN1 encoding HIV-1 Tat and pNL4-3 encoding HIV-1 [full HIV-1 genome]). HIV-1 Tat and HIV-1 inhibited Notch-1expression, with differential effects on EGFR. Notch-1 inhibition nullified Cyclin D expression with p21 induction and increased G2-M cell population in CaSki cells. On the contrary, HIV-1 infection shuts down p21 expression through interaction of Notch-1 downstream genes Hes-1-EGFR and Cyclin D for G2-M arrest, DDR response and cancer progression. This work lays foundations for future research and interventions, and therefore is necessary. Our results describe for the first time how HIV-1 Tat cancers have an aggressive nature due to the interplay between Notch-1 and EGFR signaling. Notch-1 inhibitor, DAPT used in organ cancer treatment may help rescue HIV-1 induced cancers.The illustration shows how HIV interacts with HPV-16 to induce Notch 1 suppression for cancer progression (Created with BioRender.com).The online version contains supplementary material available at 10.1007/s13337-023-00809-y.© The Author(s), under exclusive licence to Indian Virological Society 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.