Mofed Dina, Mandarino Angelo, Wu Xuhong, Lang Yuekun, Gowripalan Anjali, Kalpana Ganjam V, Prasad Vinayaka R
bioRxiv. 2024 Oct 24:2024.10.24.619504. doi: 10.1101/2024.10.24.619504.
HIV-1 subtype C viruses are responsible for 50% of global HIV burden. However, nearly all currently available reporter viruses widely used in HIV research are based on subtype B. We constructed and characterized a replication competent HIV-1 subtype C reporter virus expressing mGreenLantern. mGreenLantern sequences were inserted in-frame with ATG in HIV-1 . As controls, we employed HIV-1 , HIV-1 and HIV-1 viruses. HIV-1 (HIV-1 ) exhibited characteristics of the parental HIV-1 virus, including its infectivity in TZMbl reporter cells and replication competence in macrophages. To further characterize HIV-1 virus, we tested its responsiveness to CCL2 levels, a characteristic feature of subtype B HIV-1 that is missing in subtype C. CCL2 immunodepletion inhibited the production of HIV-1 and HIV-1 as expected, but not that of HIV-1 as previously reported. We also tested the effect of Methamphetamine, as its effect is mediated by NF-κB and since subtype C viruses carry an additional copy of NFκB. We found that methamphetamine increased the replication of all viruses tested in macrophages, however, its effect was much more robust for HIV-1 and HIV-1 . Our studies established that HIV-1 retains all the characteristics of the parental HIV-1 and can be a useful tool for HIV-1 subtype C investigations.
HIV-1 C亚型病毒导致了全球50%的HIV负担。然而，目前几乎所有广泛用于HIV研究的报告病毒都是基于B亚型的。我们构建并表征了一种表达mGreenLantern的具有复制能力的HIV-1 C亚型报告病毒。mGreenLantern序列与HIV-1中的ATG框内插入。作为对照，我们使用了HIV-1、HIV-1和HIV-1病毒。HIV-1（HIV-1）表现出亲本HIV-1病毒的特征，包括其在TZMbl报告细胞中的感染性和在巨噬细胞中的复制能力。为了进一步表征HIV-1病毒，我们测试了其对CCL2水平的反应性，CCL2水平是B亚型HIV-1的一个特征性特征，而C亚型中不存在。如预期的那样，CCL2免疫耗竭抑制了HIV-1和HIV-1的产生，但并未如先前报道的那样抑制HIV-1的产生。我们还测试了甲基苯丙胺的作用，因为其作用是由NF-κB介导的，并且由于C亚型病毒携带额外的NFκB拷贝。我们发现甲基苯丙胺增加了在巨噬细胞中测试的所有病毒的复制，然而，其对HIV-1和HIV-1的作用更强。我们的研究表明，HIV-1保留了亲本HIV-1的所有特征，并且可以成为HIV-1 C亚型研究的有用工具。
