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Review
. 2022 May 18;14(5):1084.
doi: 10.3390/v14051084.

HIV UTR, LTR, and Epigenetic Immunity

Jielin Zhang  1 , Clyde Crumpacker  1
Affiliations
Review

HIV UTR, LTR, and Epigenetic Immunity

Jielin Zhang et al. Viruses. .

Abstract

The duel between humans and viruses is unending. In this review, we examine the HIV RNA in the form of un-translated terminal region (UTR), the viral DNA in the form of long terminal repeat (LTR), and the immunity of human DNA in a format of epigenetic regulation. We explore the ways in which the human immune responses to invading pathogenic viral nucleic acids can inhibit HIV infection, exemplified by a chromatin vaccine (cVaccine) to elicit the immunity of our genome-epigenetic immunity towards a cure.

Keywords: HIV; chromatin vaccine (cVaccine); cure; epigenetics; super enhancer.

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Conflict of interest statement

The authors declare no conflict of interest. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector. The authors plan to have provisional patent applications on some of the concepts discussed in this review.

Figures

Figure 1
Figure 1
HIV UTR and LTR. U: unique element. R: repeat element. Provirus is a metastable stage in the retroviral lifecycle. A breach of the metastable equilibrium depends on the host cell signals not the virus. Based on the knowledge of X-chromosome inactivation and the stem cell features of CD4 T-cells, the host epigenetic silencing and cART can force the provirus into a stable state—a permanent silencing, similar to the ancient human endogenous retroviruses (HERVs) resided in our DNA.
Figure 2
Figure 2
Epigenetic Immunity—a genetic immunity. A cell defends its genome against a foreign agent invasion by epigenetic immune regulations [9,10,127]. In HIV infection, the host cell protects its DNA from the viral nucleic acid attack by the epigenetic immunity, consisting of DNA methylation, histone acetylation/methylation, and non-coding RNA (ncRNA) activity. DNA methylation affects the function of double stranded DNA, histone modification affects the function of nucleosome, and ncRNA affects the function of chromatin. Each works independently but synergistically with the other two, guarding the topological structure and function of the DNA, and acting as a writer, reader, eraser, adaptor, modifier, organizer, or programmer [10,118,127]. The epigenetic factors reprogram genetic immune responses embodying gene activation, silencing, epigenetic memory, and chromatin remodeling in responding to environmental stimuli, specifically pathogenic foreign nucleic acids such as HIV.
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