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Review Articles

HIV co-receptor-tropism: cellular and molecular events behind the enigmatic co-receptor switching

, , , &
Pages 499-516 | Received 31 Dec 2020, Accepted 09 Mar 2021, Published online: 26 Apr 2021
 

Abstract

Recognition of cell-surface receptors and co-receptors is a crucial molecular event towards the establishment of HIV infection. HIV exists as several variants that differentially recognize the principal co-receptors, CCR5 and CXCR4, in different cell types, known as HIV co-receptor-tropism. The relative levels of these variants dynamically adjust to the changing host selection pressures to infect a vast repertoire of cells in a stage-specific manner. HIV infection sets in through immune cells such as dendritic cells, macrophages, and T-lymphocytes in the acute stage, while a wide range of other cells, including astrocytes, glial cells, B-lymphocytes, and epithelial cells, are infected during chronic stages. A change in tropism occurs during the transition from acute to a chronic phase, termed as co-receptor switching marked by a change in disease severity. The cellular and molecular events leading to co-receptor switching are poorly understood. This review aims to collate our present understanding of the dynamics of HIV co-receptor-tropism vis-à-vis host and viral factors, highlighting the cellular and molecular events involved therein. We present the possible correlations between virus entry, cell tropism, and co-receptor switching, speculating its consequences on disease progression, and proposing new scientific pursuits to help in an in-depth understanding of HIV biology.

Disclosure statement

The authors declare no conflict of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study.

Additional information

Funding

SB acknowledges funding from DBT [BT/HRD/NWBA/38/09/2018 and BT/PR15450/COE/34/46/2016] and DST-SERB for support. YS and GV thank joint UGC-CSIR JRF, and KM thanks DST for the WOSA fellowship. UGC-SAP, DST-FIST grants to the Department of Biochemistry, and Institution of Eminence supported project RC1-20-017 to SB and IoE to the University of Hyderabad by MHRD (F11/9/2019-U3(A) is acknowledged.

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