Genetic variant in CXCL12 gene raises susceptibility to HPV infection and squamous intraepithelial lesions development: a case-control study

Abstract

BackgroundHuman papillomavirus (HPV) is the most common sexually transmitted virus in women worldwide. The persistence of the virus may cause warts that are considered benign lesions and low or high grade intraepithelial lesions (LSIL/HSIL). Immunological system plays an important role in the resolution of infections. In this context, we highlight the chemokines, which are important regulators in the development of viral infections and inflammation. Among which CXCL12 stands out, due to its pro-inflammatory features, acting as chemoattractant recruiting immune cells. Several polymorphisms were identified in CXCL12 gene including rs1801157 in the 3′-untranslated region, which is characterized by a substitution of a guanine for an adenine.MethodsIn this study, 195 women were classified as HPV non-infected and 169 as HPV-infected. HPV-DNA was detected by polymerase chain reaction (PCR) and the polymorphism was assessed in blood cells through restriction fragment length polymorphism analysis.ResultsHPV infection was more incident in women who had more than 4 sexual partners during lifetime (p = 0.007), among those who presented lower number of pregnancies (p = 0.017). HPV was more prevalent among allele A carriers confirmed by logistic regression analysis adjusted for several confounding factors [ORADJ = 4.985; CI95% (2.85–8.72), p < 0.001]. An association between allele A carriers and HSIL development (p = 0.003) was also observed.ConclusionsIn the present study, we demonstrated that CXCL12 rs1801157 is independently associated with HPV infection and exerts influence in HSIL development, suggesting it as a promising susceptibility biomarker for HPV infection and lesions development.

The Role of Non-coding RNAs in Viral Myocarditis

“…Corsten et al found that CVB3 infection promoted the miR-221/-222 expression in cardiac tissue. Further study demonstrated that miR-221/-222 could inhibit ETS1/2, interferon regulatory factor 2 (IRF2), Bcl-2-like protein 11 (BCL2L11), Thymocyte selection-associated high-mobility group box (TOX), BCL-2-modifying factor (BMF), and CXC chemokine ligand 12 (CXCL12) As we all know, those target genes are important in viral replication and inflammation (Welsh, 1986 ; Bosselut et al, 1990 ; Sieweke et al, 1998 ; Posada et al, 2000 ; Kühl et al, 2003 ; Zhan et al, 2005 ; Russell and Garrett-Sinha, 2010 ; Cheng et al, 2011 ; Johansson et al, 2011 ; Tanaka-Nakanishi et al, 2014 ; Okuyama et al, 2018 ). The in-vitro study confirmed that miR-221/-222 inhibited inflammation through those IRF2, CXCL12 and TOX in CVB3 infection (Corsten et al, 2015 ).…”

Cross-Sectional Analysis of Human Papillomavirus Infection and Cytological Abnormalities in Brazilian Women

“…In fact, sociodemographic data show the social inequalities associated with the high risk of HPV infection leading to cervical cancer, as the virus is more prevalent in public health facilities than in private clinics [ 25 ]. In this context, the lack of knowledge about HPV, as well as its prevention and transmission, is a factor that should be considered in women with less education [ 26 ].…”

The Chemokine System in Oncogenic Pathways Driven by Viruses: Perspectives for Cancer Immunotherapy

“…First, CXCL12 expression, absent in healthy epithelia, was observed in HPV skin or mucosal lesions [124], suggesting that HPV oncogenes can alter the expression of the chemokine and its receptors CXCR4 and ACKR3 as they do in cultured keratinocytes [125]. Then, expression of the WHIM-associated genetic variant of CXCR4 is capable of biasing the HPV life cycle toward an oncogenic program, as demonstrated in three dimensional (3D) organotypic epithelial cultures [126] in support of its role as a susceptibility co-factor for HPV-induced pathogenesis, as proposed also for genetic variants of CXCL12 [127]. Second, mice harboring WHIM-associated Cxcr4 GOF mutation models the panleukopenia reported in patients [128] in support of critical functions endowed by CXCR4 in immune-hematological processes, including homeostatic immunity, driven by a network of skin-resident immune cells [129].…”