Multiple NF-kappa B Sites in HIV-1 Subtype C Long Terminal Repeat Confer Superior Magnitude of Transcription and Thereby the Enhanced Viral Predominance

作者：Bachu Mahesh; Yalla Swarupa; Asokan Mangaiarkarasi; Verma Anjali; Neogi Ujjwal; Sharma Shilpee; Murali Rajesh V; Mukthey Anil Babu; Bhatt Raghavendra; Chatterjee Snehajyoti; Rajan Roshan Elizabeth; Cheedarla Narayana; Yadavalli Venkat S; Mahadevan Anita; Shankar Susarla K; Rajagopalan Nirmala; Shet Anita; Saravanan Shanmugam; Balakrishnan Pachamuthu; Solomon Suniti; Vajpayee Madhu; Satish Kadappa Shivappa; Kundu Tapas K; Jeang Kuan Teh; Ranga Udaykumar^*

来源：Journal of Biological Chemistry, 2012, 287(53): 44714-44735.

DOI：10.1074/jbc.M112.397158

Wedemonstrate that at least three different promoter variant strains of HIV-1 subtype C have been gradually expanding and replacing the standard subtype C viruses in India, and possibly in South Africa and other global regions, over the past decade. The new viral strains contain an additional NF-kappa B, NF-kappa B-like, or RBEIII site in the viral promoter. Although the acquisition of an additional RBEIII site is a property shared by all the HIV-1 subtypes, acquiring an additional NF-kappa B site remains an exclusive property of subtype C. The acquired kappa B site is genetically distinct, binds the p50-p65 heterodimer, and strengthens the viral promoter at the levels of transcription initiation and elongation. The 4-kappa B viruses dominate the 3-kappa B %26quot;isogenic%26quot; viral strains in pairwise competition assays in T-cell lines, primary cells, and the ecotropic human immunodeficiency virus mouse model. The dominance of the 4-kappa B viral strains is also evident in the natural context when the subjects are coinfected with kappa B-variant viral strains. The mean plasma viral loads, but not CD4 counts, are significantly different in 4-kappa B infection suggesting that these newly emerging strains are probably more infectious. It is possible that higher plasma viral loads underlie selective transmission of the 4-kappa B viral strains. Several publications previously reported duplication or deletion of diverse transcription factor-binding sites in the viral promoter. Unlike previous reports, our study provides experimental evidence that the new viral strains gained a potential selective advantage as a consequence of the acquired transcription factor-binding sites and importantly that these strains have been expanding at the population level.

• 出版日期2012-12-28
• 单位河北医科大学