The Examination of Viral Characteristics of HIV-1 CRF07_BC and Its Potential Interaction with Extracellular Galectin-3

Abstract

HIV-1 CRF07_BC is a B’ and C subtype recombinant emerging virus and many of its viral characteristics remain unclear. Galectin-3 (Gal3) is a β-galactose binding lectin that has been reported as a pattern recognition receptor (PRR) and is known to mediate adhesion between cells and microbes. This study aims to examine the viral characteristics of HIV-1 CRF07_BC virus and the role of extracellular galectin-3 in HIV-1 CRF07_BC infection. A total of 28 HIV-1+ injecting drug users (IDUs) were recruited and 24 (85.7%) were identified as HIV-1 CRF07_BC. Results indicate that significant higher serum galectin-3 was measured in CRF07_BC infected patients and CRF07_BC infection triggered significant galectin-3 expression (p < 0.01). Viral characteristics demonstrate that CRF07_BC virions display a higher level of envelope gp120 spikes. The virus infectivity assay demonstrated that co-treatment with galectin-3 significantly promoted CRF07_BC attachment and internalization (p < 0.01). A co-immunoprecipitation assay showed that pulldown galectin-3 co-precipitated both CD4 and gp120 proteins. Results from an enzyme-linked immunosorbent assay (ELISA) indicate that the galectin-3 promoting effect occurs through enhancement of the interaction between gp120 and CD4. This study suggests that CRF07_BC was predominant in HIV-1+ IDUs and CRF07_BC utilized extracellular galectin-3 to enhance its infectivity via stabilization of the gp120-CD4 interaction.

Diagnostic Significance of Serum Galectin-3 in Hospitalized Patients with COVID-19—A Preliminary Study

“…Increased serum galectin-3 has been observed in patients with varicella-zoster virus infection and patients with herpes zoster neuralgia and post-herpetic neuralgia presented with higher concentrations [17]. In human immunodeficiency virus infection, galectin-3 has been shown to support the attachment of the virus to macrophages and CD4+ T cells [19,34]. Galectin-3 was induced in hepatitis B and C infections [35][36][37].…”

“…A spectrum of complications observed in patients with coronavirus disease 2019 (COVID- 19) is not restricted to the widely recognized severe acute respiratory syndrome. The complications may include exacerbation of comorbidities, coagulopathies, bacterial superinfections with increased risk of sepsis, and multiple organ failure (MOF) [1].…”

“…It is found in spleen, stomach, colon, liver, kidney, heart, uterus, ovary, pancreas, and lungs (alveolar cells) [15,17]. Galectin-3 has been previously studied in relation to several viral infections in human, including human immunodeficiency virus, herpesvirus-1 infection, influenza, early herpes zoster neuralgia, and postherpetic neuralgia [15,[17][18][19][20].…”

Comparison of the Immunogenicity of HIV-1 CRF07_BC Gag Antigen With or Without a Seven Amino Acid Deletion in p6 Region

“…Mutations at the Alix-binding site of the p6 region led to impaired HIV-1 replication and the decreased efficiency of viral budding in various cell types ( 12 ). A previous study revealed that the expression of Galectin-3 was upregulated in response to HIV-1 CRF07_BC infection ( 31 ), and the endogenous Galectin-3 facilitated the binding of Alix-Gag p6 complex to promote HIV-1 budding ( 32 ). However, this promoting effect could be disrupted because of the seven amino acid deletion in the Gag p6 region ( 33 ).…”

Virus Hijacks Host Proteins and Machinery for Assembly and Budding, with HIV-1 as an Example

“…Recently, some cellular proteins have been reported to facilitate HIV virus replication, for example, galectin-3 (Gal3), a chimera type of the galectin family, exerting both endogenous and exogenous regulatory capabilities to various cellular immunol functions and even infectious status [ 36 , 37 ] ( Figure 1 B). The up-regulation of Gal3 was reported during HIV-1 infection by the Tat protein binding to the Gal3 expression promoter [ 38 ].…”