Host-HIV-1 Interactome: A Quest for Novel Therapeutic Intervention

Abstract

The complex nature and structure of the human immunodeficiency virus has rendered the cure for HIV infections elusive. The advances in antiretroviral treatment regimes and the development of highly advanced anti-retroviral therapy, which primarily targets the HIV enzymes, have dramatically changed the face of the HIV epidemic worldwide. Despite this remarkable progress, patients treated with these drugs often witness inadequate efficacy, compound toxicity and non-HIV complications. Considering the limited inventory of druggable HIV proteins and their susceptibility to develop drug resistance, recent attempts are focussed on targeting HIV-host interactomes that are essential for viral reproduction. Noticeably, unlike other viruses, HIV subverts the host nuclear pore complex to enter into and exit through the nucleus. Emerging evidence suggests a crucial role of interactions between HIV-1 proteins and host nucleoporins that underlie the import of the pre-integration complex into the nucleus and export of viral RNAs into the cytoplasm during viral replication. Nevertheless, the interaction of HIV-1 with nucleoporins has been poorly described and the role of nucleoporins during nucleocytoplasmic transport of HIV-1 still remains unclear. In this review, we highlight the advances and challenges in developing a more effective antiviral arsenal by exploring critical host-HIV interactions with a special focus on nuclear pore complex (NPC) and nucleoporins.

Network-Based Analysis of OMICs Data to Understand the HIV–Host Interaction

“…Macromolecules, which are part of cell defense mechanisms and prevent viral infection, called host restriction factors (HRFs). During the HIV attack, several HRFs interfere with viral replication at different steps (Shukla and Chauhan, 2019). For instance, cytidine deaminase, APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G) induces lethal hypermutations (deamination of C to U) in the HIV genome, which are detrimental to viral replication.…”

“…For instance, cytidine deaminase, APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G) induces lethal hypermutations (deamination of C to U) in the HIV genome, which are detrimental to viral replication. For more information on HDFs and HRFs see the reviews (Yamashita and Engelman, 2017;Chen et al, 2018;Engelman and Singh, 2018;Shukla and Chauhan, 2019).…”

Use of Integrative Interactomics for Improvement of Farm Animal Health and Welfare: An Example with Fescue Toxicosis

“…into single, interpretable outputs, allowing an evaluation of the integrome through integrative interactomics [ 21 ]. Traditionally, interactomics is a broad, yet well-established field focused on mRNA-protein [ 22 ] and/or protein-protein [ 23 ] interactions within a large spectrum of biological systems and disorders [ 24 , 25 , 26 ]. To contrast this view of the interactome, herein we have defined the integrome as the integration of multi-‘omics data sets through integrative interactomics, allowing for the description of systemic biological interactions and multi-organ-integrative responses to internal or external variables.…”

Probing the Importance of the G-Quadruplex Grooves for the Activity of the Anti-HIV-Integrase Aptamer T30923

“…Nowadays, about 35 million people are infected with HIV worldwide and considering 2 million new infections and about 1.6 million deaths from this disease per year, AIDS is still a global emergency. The development of highly efficient anti-retroviral drugs has allowed most infected people to live with HIV as a chronic disease [1]. However, emergent drug resistance highlights the need to develop further effective unconventional ligand molecules, for example, aptamers or monoclonal antibodies.…”