Infectious RNA: Human Immunodeficiency Virus (HIV) Biology, Therapeutic Intervention, and the Quest for a Vaccine.

Yasemin van Heuvel,Jörn Stitz,Jamila Franca Rosengarten,Stefanie Schatz

doi:10.3390/toxins14020138

Yasemin van Heuvel, Jörn Stitz + Show 2 more

Open Access

https://doi.org/10.3390/toxins14020138

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Abstract

Different mechanisms mediate the toxicity of RNA. Genomic retroviral mRNA hijacks infected host cell factors to enable virus replication. The viral genomic RNA of the human immunodeficiency virus (HIV) encompasses nine genes encoding in less than 10 kb all proteins needed for replication in susceptible host cells. To do so, the genomic RNA undergoes complex alternative splicing to facilitate the synthesis of the structural, accessory, and regulatory proteins. However, HIV strongly relies on the host cell machinery recruiting cellular factors to complete its replication cycle. Antiretroviral therapy (ART) targets different steps in the cycle, preventing disease progression to the acquired immunodeficiency syndrome (AIDS). The comprehension of the host immune system interaction with the virus has fostered the development of a variety of vaccine platforms. Despite encouraging provisional results in vaccine trials, no effective vaccine has been developed, yet. However, novel promising vaccine platforms are currently under investigation.

Highlights

Genome and Virion StructureThe RNA genome (gRNA) of human immunodeficiency virus (HIV)-1, with approximately 9 kb, is considerably small. it contains all necessary information to synthesize all 15 proteins needed for replication and assembly of new virions in the infected host cells [14,15]
Research Group Pharmaceutical Biotechnology, Faculty of Applied Natural Sciences, TH Köln—University of Applied Sciences, Chempark Leverkusen, Kaiser-Wilhelm-Allee, 51368 Leverkusen, Germany; Institute of Technical Chemistry, Leibniz University Hannover, Callinstraße 3-9, 30167 Hannover, Germany
The long terminal repeats (LTRs) are distinguished into cis-acting regulatory elements, namely, U3, R, and U5 regions followed by the packaging signal Psi (ψ)

Summary

Genome and Virion Structure

The RNA genome (gRNA) of HIV-1, with approximately 9 kb, is considerably small. it contains all necessary information to synthesize all 15 proteins needed for replication and assembly of new virions in the infected host cells [14,15]. Including the viral promoter—for gene expression, integration, and reverse transcription and are divided into the U3, R, and U5 elements [10]. The R element contains the trans-acting responsive region (TAR), forming a RNA stem-loop structure that plays an important role in viral replication, i.e., the activation of transcription [17,18]. Tat and Rev are indispensable for viral replication, accumulate within the host cell nucleus and bind to their cognate mRNA structures, namely, the Rev-responsive element (RRE) and TAR. 30 -long terminal repeats that that contain thethe viral promoter requiredfor forrereverse verse transcription, integration, and gene expression. The LTRs are distinguished into cis-acting regulatory elements, namely, U3, R, and U5 regions followed by the packaging signal Psi (ψ).

Receptors and Cell Entry

Genome Integration

Cytoxicity of HIV Infection

Interplay of HIV and Immune Response—Implications for Vaccine Development

HIV Clinical Vaccine Trials

Outlook