# Comprehensive Insights into the Molecular Basis of HIV Glycoprotein  
[PERSON]  
1 Department of Management, Bar-Ilan University, Ramat Gan 5290002, Israel; [EMAIL_ADDRESS] (H.M.); [EMAIL_ADDRESS] (A.Y.R.)  
2  
[PERSON]  
1 Department of Management, Bar-Ilan University, Ramat Gan 5290002, Israel; [EMAIL_ADDRESS] (H.M.); [EMAIL_ADDRESS] (A.Y.R.)  
2  
[PERSON]  
1 Department of Management, Bar-Ilan University, Ramat Gan 5290002, Israel; [EMAIL_ADDRESS] (H.M.); [EMAIL_ADDRESS] (A.Y.R.)  
2  
Footnote 1: email: {[[http://www.mdpi.com/journal/applsci/appl/2019/](http://www.mdpi.com/journal/applsci/appl/2019/)]([http://www.mdpi.com/journal/applsci/appl/2019/](http://www.mdpi.com/journal/applsci/appl/2019/))  
infection has significantly impacted the economy, as the virus frequently affects individuals during their most economically productive years. The extensive repercussions on public health and overall well-being are immeasurable [1].  
HIV is a diploid, C-type enveloped retrovirus belonging to the Lentivirus genus, characterized by two positive-sense single-stranded RNA genomes [5]. HIV-1, known for its high infectivity and role in driving the pandemic, along with HIV-2, is classified within the Retroviridae family. These viruses possess a unique trait that defies the central dogma of molecular biology. Specifically, upon infection, viral RNA genomes are initially reverse-transcribed into DNA. Subsequently, these DNA copies integrate into the host genome, establishing persistent infections. As long as the host cell remains viable, both viral genomic RNA (vRNA) and messenger RNA (mRNA) continue to be transcribed from the integrated viral genome [5; 6]. Therefore, lentivirusves exhibit a broad spectrum of cellular tropism, enabling replication across various cell types. Beyond non-primate lentivirusises, such as those impacting fibroblasts and macrophages, HIV can infect a myriad of cell types, as evidenced by in vitro investigations, including but not limited to astrocytes, oligodendrocytes, microglia, in a lower proportion of neurons [7; 8], bowel mucosal cells, B cells, CD8+ T cells, cervical cells, eosinophils, and others [9]. Conversely, in vivo, HIV predominantly targets and establishes reservoirs in CD4+ T lymphocytes, cells of the macrophage lineage, and dendritic cells [10; 11; 12; 13]. While there is evidence of HIV involvement in trans-infection processes, the relevance of in vitro findings to in vivo infection for other cell types remains unclear.  
HIV predominantly targets cells expressing CD4 receptors, including helper T cells, CD8+ T cells, eosinophils, macrophages, and neutrophils. The CD4 receptor typically engages major histocompatibility complex (MHC) molecules on the surfaces of adjacent cells under normal conditions [10; 14]. Furthermore, the CD4 receptor is an endogenous ligand for MHC class II molecules, enhancing the interaction between antigen-presenting cells and CD4+ T lymphocytes. This interaction is stabilized by the engagement of protein kinase molecules, transmitting signals to the cytoplasmic domains of CD4 [15; 16; 17; 18; 19]. The outer envelope glycoprotein of HIV, gp120, engages with host cell CD4 receptors. Following this interaction, two host cell components, known as coreceptors, namely, CXCR4 (C-X-C Chemokine Receptor 4) and CCR5 (CC chemokine receptor 5), trigger the exposure of the gp41 fusogenic components by gp120. This exposure facilitates the fusion of the host cell and viral membranes [20; 21; 22].  
Given the vital role of glycoproteins in virus entry, this review seeks to provide a comprehensive analysis of the structural features of HIV entry proteins, explicitly focusing on gp120 and gp41 and exploring their functional roles in the viral entry process. By examining the detailed architecture of these proteins, the paper aims to elucidate how their structural properties facilitate HIV's ability to invade host cells, thereby enhancing our understanding of the mechanisms underlying viral infection.