Role of Herpes Simplex Virus Type-1 (HSV-1) in Modulating VEGF-A Expression Among Iraqi Patients Receiving Chemotherapy: A Cross-Sectional Molecular Study

Abstract

Background: Herpes simplex virus 1 (HSV-1) establishes lifelong latency with periodic reactivation, and is of particular concern in immunocompromised patients, such as those receiving treatment with chemotherapy. Experimental data suggest that upon infection, HSV-1 induces the expression of vascular endothelial growth factor A (VEGF-A), a key mediator of angiogenesis and inflammation. However, the link between HSV-1 reactivation and physiological or systemic VEGF-A in patients receiving oncological therapy have not been examined broadly.

Methods: A cross-sectional molecular study to investigate the relationship between HSV-1 reactivation and VEGF-A expression in Iraqi chemotherapy patients.

Methods: 300 subjects (200 chemotherapeutic patients and 100 control not receiving chemotherapy) were recruited. HSV-1 status was assessed by serology (IgG, IgM) and qPCR detection of viral DNA in oral swabs and plasma. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum VEGF-A concentrations and reverse transcription qPCR was performed to quantify peripheral blood mononuclear cells levels of VEGFA mRNA. A multivariable linear regression was conducted to determine the independent relationship between positivity for HSV-1 DNA and log-transformed VEGF-A levels while controlling for demographic, clinical, and immunological variables.

Results: HSV-1 DNA was found in 18% of patients undergoing chemotherapy versus 5% of controls (p < 0.001). Serum VEGF-A levels in chemotherapy patients were 

significantly higher than controls (median 412 according to 221 pg/mL; p < 0.001). In chemotherapy patients, individuals who were positive for HSV-1 DNA had significantly higher serum VEGF-A (median 712 with 368 pg/mL, p < 0.001) and increased expression of VEGFA mRNA (median fold change 3.94 compare with 1.63, p < 0.001). Oral viral load positively correlated with serum VEGF-A (Spearman ρ = 0.58, p < 0.001). In a multivariable analysis, positivity for HSV-1 DNA remained independently associated with higher log (VEGF-A) (β = 0.41, 95% CI 0.28–0.54, p < 0.001).

Conclusions: Reactivation of HSV-1 is independently correlated with enhanced VEGF-A expression in un-females and non-HSV infected chemotherapy doomed fatalities. This observation hinted that viral reactivation upon immune suppression might drive systemic angiogenic and inflammatory signaling. The clinical implications of HSV-1–mediated VEGF-A upregulation in oncology settings warrant examination in prospective studies. In the state of virus reactivation, qPCR was used to quantify HSV-1 and VEGF-A expression level.