Kamish D. Marrero
Ying Dang
Qiujia Shao
Xiangxu Jia
Bindong Liu

Universidad Central del Caribe, School of Medicine, Bayamón, Puerto Rico
Meharry Medical College, Center for AIDS Health Disparities Research, Department of Microbiology, Immunology and Physiology, Nashville, Tennessee

Introduction

Human immunodeficiency virus type 1 (HIV-1) is predominantly transmitted through mucosal surfaces, such as the genital and rectal mucosa, making these the primary sites of infection. However, oral mucosal transmission remains rare, and the mechanisms underlying this rarity are poorly understood. Previous work in our lab demonstrated that a cell wall component from the oral commensal bacterium Streptococcus cristatus (termed CC5A) inhibits HIV-1 replication in THP-1 cells, a human monocytic cell line that is targeted by this virus. However, the mechanism by which CC5A inhibits HIV-1 replication remains largely unknown. In this study, we show that CC5A downregulates the surface expression of the chemokine receptor CXCR4, thereby reducing the probability of HIV entry into host cells.

Methods

THP-1 cells were treated with CC5A overnight, followed by monitoring the overall and surface expression of CXCR4 using flow cytometry. Additionally, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to measure CXCR4 mRNA expression, confirming that overall CXCR4 mRNA expression showed no significant change compared to untreated THP-1 cells.

Results

Flow cytometry results revealed that CXCR4 surface expression was reduced in CC5A-treated samples, while the overall CXCR4 expression remained unchanged. Data also indicated that CC5A had no effect on the overall and surface expression of the CD4 receptor. qRT-PCR confirmed that CXCR4 mRNA expression showed no significant change compared to untreated THP-1 cells.

Conclusions

Given that HIV requires at the cell membrane the presence of both CD4 receptor and co-receptors such as CXCR4 to infect target cells, the reduction of CXCR4 cell surface expression decreases the likelihood of HIV entry into the host cell. This finding provides insight into a potential mechanism underlying the rarity of oral mucosal HIV transmission and highlights the role of commensal bacteria in modulating host susceptibility to viral infections.

Acknowledgments

This research was supported by NIAID grants R25AI164610 and P30AI117970.