Prevalence Of Virus Infection Research Articles

Computational Evaluation of Abrogation of HBx-Bcl-xL Complex with High-Affinity Carbon Nanotubes (Fullerene) to Halt the Hepatitis B Virus Replication.

Hepatitis B virus (HBV) is the world’s most prevalent chronic viral infection. More than 350 million individuals are chronic carriers of the virus, with an estimated 2 billion infected persons. For instance, the role of HBx protein in attachment and infection is very obvious and consequently deemed as an important druggable target. Targeting the interface and discovering novel drugs greatly advanced the field of therapeutics development. Therefore, in the current study, HBx to Bcl-xL is abrogated on high-affinity carbon nanotubes using computational structural biology tools. Our analysis revealed that among the total 62 carbon fullerenes, only 13 compounds exhibited inhibitory activity against HBx, which was further confirmed through IFD-based rescoring. Structural dynamics investigation revealed stable binding, compactness, and hydrogen bonds reprogramming. Moreover, the binding free energy calculation results revealed that the top hits1-4 possess the total binding energy of −54.36 kcal/mol (hit1), −50.81 kcal/mol (hit2), −47.09 kcal/mol (hit3), and −45.59 kcal/mol for hit4. In addition, the predicted KD values and bioactivity scores further validated the inhibitory potential of these top hits. The identified compounds need further in vitro and in vivo validation to aid the treatment process of HBV.

Morphological response and genetic variability of four species of chili pepper (Capsicum spp.) under infection of pepper yellow leaf curl virus

Abstract. Sayekti TWDA, Syukur M, Hidayat SH, Maharijaya A. 2021. Morphological response and genetic variability of four species of chili pepper (Capsicum spp.) under infection of pepper yellow leaf curl virus. Biodiversitas 22: 4758-4765. Chili pepper has various types and species, but only five known species are commonly used and consumed. Most cultivated chili is susceptible to various plant diseases, one of which is Pepper yellow leaf curl disease (PYLCD) caused by Pepper yellow leaf curl virus (PYLCV) (Begomovirus, Geminiviridae). To control PYLCD, resistant variety assembly is required to prevent virus infection in cultivated plants. From this research, testing on four chili species is expected to provide information regarding the resistance and performance of chili peppers to conditions infected with PYLCV. This study was conducted at Dramaga Bogor, West Java, Indonesia in two experimental units: planting under virus-free conditions (as control) and virus-infected conditions. Each experimental unit was carried out using a single factor Randomized Complete Block Design (RCBD) with three replications. Twenty-nine genotypes of chili pepper were used consisted of four species, including C. annuum, C. frutescens, C. chinense, and C. baccatum. Of the 29 genotypes tested, thirteen genotypes in the resistant, nine genotypes in moderate resistant, two genotypes in moderate susceptible, three genotypes in the Susceptible, and two genotypes in the highly susceptible category. The heritability, genotypic coefficient of variance (GCOV) and phenotypic coefficient of variance (PCOV) value obtained from testing for all characters is high, ranging from 65.16-99.12%, 14.87-82.60%, and 15.77-84.45%, respectively. Most of the genotypes from C. chinense showed good resistance to PYLCV. In general, by considering the category of the resistance level and other characters such as productivity, ‘Jolokia’ (C. chinense), ‘Anies’ (C. annuum) and ‘Bonita’ (C. frutescens) can be ascertained as potential candidate sources of resistance to PYLCV.

Natural Products and Their Derivatives against Human Herpesvirus Infection.

Herpesviruses establish long-term latent infection for the life of the host and are known to cause numerous diseases. The prevalence of viral infection is significantly increased and causes a worldwide challenge in terms of health issues due to drug resistance. Prolonged treatment with conventional antiviral drugs is more likely to develop drug-resistant strains due to mutations of thymidine nucleoside kinase or DNA polymerase. Hence, the development of alternative treatments is clearly required. Natural products and their derivatives have played a significant role in treating herpesvirus infection rather than nucleoside analogs in drug-resistant strains with minimal undesirable effects and different mechanisms of action. Numerous plants, animals, fungi, and bacteria-derived compounds have been proved to be efficient and safe for treating human herpesvirus infection. This review covers the natural antiherpetic agents with the chemical structural class of alkaloids, flavonoids, terpenoids, polyphenols, anthraquinones, anthracyclines, and miscellaneous compounds, and their antiviral mechanisms have been summarized. This review would be helpful to get a better grasp of anti-herpesvirus activity of natural products and their derivatives, and to evaluate the feasibility of natural compounds as an alternative therapy against herpesvirus infections in humans.

In vitro and in vivo efficacy of Metformin against dengue

Dengue is a prevalent mosquito-borne viral infection in the tropical and sub-tropical regions. Its potential to progress into severe, life-threatening disease, has pressed the research community to develop safe, effective and affordable antivirals. Metformin (MET), a first-line antidiabetic drug and indirect AMP-activated protein kinase (AMPK) activator, has recently emerged as a potential anti-DENV therapeutic candidate, based on some experimental evidence supporting anti-DENV activity in vitro and widely reported anti-inflammatory properties. Here, we examined MET in vitro activity against the four DENV serotypes and in two different mammalian cell lines. MET displayed a poor anti-DENV activity in BHK-21 cells with IC50 in the mM range, which was associated with increased p-AMPKα levels, thereby supporting that MET antiviral activity is mediated through AMPK activation. In contrast, MET exerted a pro-DENV activity in Vero cells that did not correlate with increased AMPK activation, suggesting AMPK-independent effects. Treatment with compound 991, a direct AMPK activator, led to reduced viral titers against all four serotypes and across both mammalian cell lines. In vivo, oral administration of MET did not reduce viremia titers in an asymptomatic mouse model, neither did it improve disease severity and progression in a mouse model of severe dengue. Instead, high dose regimen worsened disease outcome as evidenced by increased mortality, higher viremia and hyper-inflammation. Therefore, while AMPK may represent a potential host target, MET does not seem to hold great promise as a pan-serotype anti-dengue drug.

A Screening for Virus Infections in Eight Herds of Semi-domesticated Eurasian Tundra Reindeer (Rangifer tarandus tarandus) in Norway, 2013-2018.

Background: Previous serological screenings have indicated that Eurasian semi-domesticated tundra reindeer (Rangifer tarandus tarandus) in Finnmark, Northern Norway, are exposed to alphaherpesvirus, gammaherpesvirus and pestivirus. Alphaherpesvirus (i.e., Cervid herpesvirus 2; CvHV2) has been identified as the transmissible component of infectious keratoconjunctivitis (IKC). Limited knowledge exists on the presence and prevalence of virus infections in other herding regions in Norway, which are hosting ~67,000 semi-domesticated reindeer and have contact with other species and populations of wildlife and livestock than those present in Finnmark.Methods: Blood samples (n = 618) were obtained over five winter seasons (2013–2018), from eight different herds representing summer pasture districts in Tana, Lakselv, Tromsø, Lødingen, Hattfjelldal, Fosen, Røros, and Filefjell, distributed from North to South of the reindeer herding regions in Norway. Blood samples were investigated for specific antibodies against five viral pathogen groups, alphaherpesvirus, gammaherpesvirus (viruses in the malignant catarrhal fever group; MCFV), pestivirus, bluetongue virus (BTV), and Schmallenberg virus (SBV), by using commercial multispecies serological tests (ELISA). In addition, swab samples obtained from the nasal mucosal membrane from 486 reindeer were investigated by PCR for parapoxvirus-specific DNA.Results: Antibodies against aphaherpesvirus and MCFV were found in all eight herds, with a total prevalence of 42% (range 21–62%) and 11% (range 2–15%), respectively. Anti-Pestivirus antibodies were detected in five of eight herds, with a total prevalence of 19% (range 0–52%), with two of the herds having a particularly high seroprevalence. Antibodies against BTV or SBV were not detected in any of the animals. Parapoxvirus-specific DNA was detected in two animals representing two different herds in Finnmark.Conclusions: This study confirmed that alphaherpesvirus and MCFV are enzootic throughout the geographical reindeer herding regions in Norway, and that pestivirus is present in most of the herds, with varying seroprevalence. No exposure to BTV and SBV was evident. This study also indicated that semi-domesticated reindeer in Finnmark are exposed to parapoxvirus without disease outbreaks being reported from this region.

Neurosyphilis Presenting with Optic Neuritis

The incidence of syphilis has greatly reduced in the severity of affected individuals due to the early treatment with antibiotics. However, due to the increase in the prevalence of human immunodeficiency virus (HIV) infection, it has also caused a concurrent rise in the number of neurosyphilis patients. Most common ocular manifestations include uveitis, interstitial keratitis, and vasculitis. A healthy 28-years old man presented with a progressive blurring of vision in the right eye for one month. It was his second episode. The first episode occurred 4 months back which resolved spontaneously without treatment. Vision in the right eye was 6/18. The pupil was dilated and the relative afferent pupillary defect was positive. Fundus examination showed a hyperemic swollen right optic disc with blurred margins and no macular fan or star. Vision, anterior segment, and fundus were normal in the left eye. After the investigations, he was diagnosed as a case of neurosyphilis with optic neuritis. He was treated with intravenous penicillin for two weeks followed by oral penicillin for three weeks. Vision in the right eye improved to 6/6; the optic disc swelling resolved with clear margins. He maintained good vision during the follow-up of six months. Early referral to an ophthalmologist upon suspicion of syphilis, detailed evaluation, and immediate treatment is mandatory to prevent permanent vision loss in these patients.

Molecular Investigation of Human Cytomegalovirus and Epstein-Barr virus in Glioblastoma Brain Tumor: A Case-Control Study in Iran

Glioblastoma multiforme is the most invasive and lethal form of brain cancer with unclear etiology. Our study aimed to investigate the molecular prevalence of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in patients with glioblastoma multiforme (GBM). This case-control study was conducted on 42 FFPE brain tumor samples from GBM patients and 42 brain autopsies from subjects without neurological disorders. The presence of EBV and HCMV DNA was determined, using PCR and nested-PCR assays, respectively. HCMV DNA was detected in 3 out of 42 (7.1%) of GBM samples and was absent from the control group (p = 0.07). Importantly, EBV DNA was detected in 9 out of 42 (21.4%) brain tissue specimens of GBM subjects, but again in none of the control group (p = 0.001). Our findings indicate that infection with EBV is associated with GBM.

Prognosis of Laboratory-Confirmed Influenza and Respiratory Syncytial Virus in Acute Heart Failure.

Concomitant respiratory viral infections may influence clinical outcomes of acute decompensated heart failure (ADHF) but this association is based on indirect observation. The aim of this study was to evaluate the prevalence and impact of laboratory-confirmed influenza or respiratory syncytial virus (RSV) infection on outcomes in patients hospitalised for ADHF. Prospective cohort of patients hospitalised for ADHF with systematic influenza and RSV screening using real-time PCR on nasopharyngeal swabs. The primary outcome was all-cause mortality or readmission at 90 days. Among 803 patients with ADHF, 196 (24.5%) patients had concomitant flu-like symptoms of influenza. PCR was positive in 45 patients (27 for influenza, 19 for RSV). At 90 days, PCR positive patients had lower rates of all-cause mortality or readmission as compared to patients without flu-like symptoms (HR 0.40, 95% CI 0.18–0.91, p = 0.03), and non-significantly less all-cause mortality (HR 0.30, 95% CI 0.04–2.20, p = 0.24), or HF-related death or readmission (HR 0.36, 95% CI 0.13–0.99, p = 0.05). The prevalence of influenza or RSV infection in patients admitted for ADHF was low and associated with less all-cause mortality and readmission. Concomitant viral infection with ADHF may not in itself be a predictor of poor outcomes. (ClinicalTrials.gov NCT02444416).

SEROEPIDEMIOLOGICAL SURVEY OF CAPRINE ARTHRITIS ENCEPHALITIS VIRUS AND BLUETONGUE VIRUS IN GOAT HERDS FROM PARAIBA STATE, NORTHEASTERN BRAZIL

Caprine arthritis encephalitis (CAE) and bluetongue (BT) are viral diseases affecting goats and sheep, respectively, worldwide. Both diseases are characterized by being slow and progressive, causing a variety of clinical signs and determining economic and production losses. The objective of this study was to evaluate the seroprevalence of CAE and BT and its associated factors in dairy and beef goat herds in the state of Paraíba, Northeast Brazil. In total, 6.4% and 1.8% of the animals were positive for caprine arthritis encephalitis and bluetongue, respectively, by Agarose Gel Immunodiffusion assay (AGID). No significant statistical association was found between diseases and risk factors, herd size, age, gender, and type of management in most animals evaluated. The risk factors, production system and grazing of multispecies can influence the prevalence of viral infections in goats in the state of Paraíba.

Forest-bathing and physical activity as weapons against COVID-19: a review.

Strengthening the immune system in order to better withstand the threat of COVID-19 is an important way to ensure the protection of our health against the current pandemic associated with SARS-CoV-2. There are many ways to achieve this, but with current circumstances, certain modalities stand out as being the most valid and are certainly worth greater consideration. Here we review the effects that particular immuno-strengthening activities can have on limiting the severity of COVID-19 disease as well as preventing virus infection. Physical activity, in particular, should not be discounted as an important method of prevention of viral diseases as it triggers many biological processes within the human body which in turn lead to heightened natural defences against viral infections. When exercise is performed in forested areas, these protective health benefits may be increased since many plant species emit biogenic volatile compounds (VOCs) which, when inhaled, have many protective properties. These VOCs have been shown in particular to have immunostimulatory effects on the human body and, thus, they could be of use in the prevention and/or treatment of COVID-19. Being amongst trees may also help to alleviate stress and anxiety, lowering cortisol levels and consequently helping the proper functioning of the immune system. In the following work, we have performed an analysis of the available scientific literature which looks at the effects of physical exercise as well as ‘forest-bathing’ on the immune system’s ability to fight disease, especially of course as it relates to COVID-19. Our review aims at shedding light on the benefits of exercising outdoors in green areas and suggests reforestation as a protective measure against future outbreaks.

Prevalence and risk factors of bluetongue virus infection in sheep and goats in China: A systematic review and meta-analysis

Bluetongue is a viral disease transmitted by the bite of bloodsucking insects, which mainly occurs in sheep, goats, and cattle. Bluetongue is characterized by fever, leukopenia, and severe catarrhal inflammation of the oral and gastrointestinal mucosa. The present study aimed to evaluate and analyze the prevalence of bluetongue and its associated risk factors in sheep and goats in China. We collected 59 publications from 1988 to 2019 through searches at ScienceDirect, PubMed, the Chongqing VIP Chinese journal database, Wanfang database, and Chinese Web of knowledge. In these studies, a total of 123,982 sheep and goats across 7 regions of China were investigated, and the pooled prevalence of bluetongue in sheep and goats was 18.6%, as assessed using serological methods. The prevalence of bluetongue in Southern China was 30.3%, which was significantly higher than that in Northeastern China (4.7%). The prevalence of bluetongue between sheep (12.9%) and goats (28.1%) was significantly different (P < 0.05). Detection methods subgroup analysis showed that the prevalence of bluetongue was significantly higher (P < 0.05) in the others group (43.8%) than in the agar immunodiffusion (15.9%) and enzyme-linked immunosorbent assay groups (20.5%). In addition, different geographical factors (latitude range, longitude range, altitude range, average precipitation, and average temperature) could affect the prevalence. Our results suggested that bluetongue is widespread in sheep and goats, and sheep and goats in contact with insect media, such as Culicoides, or in a warm and humid environment, could have an increased prevalence of bluetongue disease. Animal disease prevention and control departments should focus on continuous monitoring of the bluetongue epidemic in sheep and goats to prevent and control outbreaks.

Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma

Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging. Nasopharyngeal carcinoma (NPC) is a distinctive cancer with poor differentiation and high prevalence of Epstein-Barr virus (EBV) infection. Here, we show that the expression of EBV latent protein LMP1 induces dedifferentiated and stem-like status with high plasticity through the transcriptional inhibition of CEBPA. Mechanistically, LMP1 upregulates STAT5A and recruits HDAC1/2 to the CEBPA locus to reduce its histone acetylation. HDAC inhibition restored CEBPA expression, reversing cellular dedifferentiation and stem-like status in mouse xenograft models. These findings provide a novel mechanistic epigenetic-based insight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.

The Correlation Between Human Immunodeficiency Virus (HIV) Infections in Pregnancy and Low Birth Weight Infants

Background: The prevalence of Human Immunodeficiency Virus (HIV) infection in pregnancy were increase in developing countries. The existence of infection interferes with the absorption of nutrients due to accumulation of inflammatory cells in the placenta can cause the infant born with low birth weight.&#x0D; Objective: The purpose of this study was to determine the correlation of HIV infections in pregnancy and low birth weight infant.&#x0D; Methods: This research used an observational analytic design with a retrospective approach. The samples were positive and negative HIV mother with their infants that hospitalized at dr. Soebandi Hospital, Jember, from August 2014 - July 2017. The data were analysed by Fisher's Exact.&#x0D; Results: This study was found 52 positive HIV mother with their infants and 52 negative HIV mother with their infants. Nine from 52 infants (17.3%) who born from positive HIV mother were low birth weight. Only 3 from 52 infants (5.8%) who born from negative HIV mother were low birth weight. Data analysis using Fisher’s Exact was obtained p value = 0.06.&#x0D; Conclusion: There was no significant correlation of HIV infections in pregnancy and low birth weight infant.

Liquid Biopsy in Cervical Cancer: Hopes and Pitfalls.

Simple SummaryCervical cancer is the fourth most common cancer in women worldwide, and its incidence is variably distributed between developed and less-resourced countries, in which socio-economic issues and religious beliefs often limit the widespread diffusion and the access to screening campaigns. In the “liquid biopsy” era, the application of non-invasive and repeatable techniques to the identification of diagnostic, prognostic, and predictive biomarkers might facilitate the management of this disease and, hopefully, improve its outcome. The purpose of this review is to explore the progress status of liquid biopsy in cervical cancer patients. Several methods are described, which include the analysis of circulating tumor cells, the search for pathogenic mutations on circulating tumor DNA, as well as the identification of circulating RNAs, focusing on their potential clinical applications and current limitations.Cervical cancer (CC) is the fourth most common cancer in women worldwide, with about 90% of cancer-related deaths occurring in developing countries. The geographical influence on disease evolution reflects differences in the prevalence of human papilloma virus (HPV) infection, which is the main cause of CC, as well as in the access and quality of services for CC prevention and diagnosis. At present, the most diffused screening and diagnostic tools for CC are Papanicolaou test and the more sensitive HPV-DNA test, even if both methods require gynecological practices whose acceptance relies on the woman’s cultural and religious background. An alternative (or complimentary) tool for CC screening, diagnosis, and follow-up might be represented by liquid biopsy. Here, we summarize the main methodologies developed in this context, including circulating tumor cell detection and isolation, cell tumor DNA sequencing, coding and non-coding RNA detection, and exosomal miRNA identification. Moreover, the pros and cons of each method are discussed, and their potential applications in diagnosis and prognosis of CC, as well as their role in treatment monitoring, are explored. In conclusion, it is evident that despite many advances obtained in this field, further effort is needed to validate and standardize the proposed methodologies before any clinical use.

Prevalence of HPV genital infection in patients with moderate-to-severe psoriasis undergoing systemic treatment with immunosuppressive agents or biologics.

Psoriasis is an immune-mediated inflammatory disease and its relationship with infection has been extensively investigated. Concern for the increased prevalence of human papilloma virus (HPV) infection in patients undergoing systemic immunomodulatory or immunosuppressive therapies for psoriasis has been gradually growing among clinicians. To evaluate the prevalence of HPV in a cohort of patients with psoriasis treated with currently available systemic, conventional and biotechnological drugs. A multi-centric prospective study was conducted in the main dermatological clinical centres of central and southern Italy. Data from 588 patients (366 males and 222 females) with moderate-to-severe psoriasis, aged ≥18 years and treated with conventional and biological drugs, were collected based on a documented history of HPV infection, a positive Papanicolaou test (Pap-test) when available, and clinical evidence of genital warts reported during consultation. Overall, 18 of 588 patients (3.6% [95%CI: 1.8-4.5]) were positive for HPV or had a history of cervical cancer. Considering anamnestic and demographic data, such as gender, age, smoking, weight and body mass index, no statistically significant differences between HPV+ and HPV- patients were found. Moreover, the eradication of HPV infection was successfully achieved using conventional treatments. The prevalence of HPV infection in patients with moderate-to-severe psoriasis, undergoing systemic treatment with immunosuppressive agents or biologics, appears to be the same as that in the general Italian population, indicating that the level of infection among such patients is acceptable.

Protamine-Controlled Reversible DNA Packaging: A Molecular Glue.

Packaging paternal genome into tiny sperm nuclei during spermatogenesis requires 106-fold compaction of DNA, corresponding to a 10-20 times higher compaction than in somatic cells. While such a high level of compaction involves protamine, a small arginine-rich basic protein, the precise mechanism at play is still unclear. Effective pair potential calculations and large-scale molecular dynamics simulations using a simple idealized model incorporating solely electrostatic and steric interactions clearly demonstrate a reversible control on DNA condensates formation by varying the protamine-to-DNA ratio. Microscopic states and condensate structures occurring in semidilute solutions of short DNA fragments are in good agreement with experimental phase diagram and cryoTEM observations. The reversible microscopic mechanisms induced by protamination modulation should provide valuable information to improve a mechanistic understanding of early and intermediate stages of spermatogenesis where an interplay between condensation and liquid-liquid phase separation triggered by protamine expression and post-translational regulation might occur. Moreover, recent vaccines to prevent virus infections and cancers using protamine as a packaging and depackaging agent might be fine-tuned for improved efficiency using a protamination control.

The Prevalence of Hepatitis C Virus (HCV) Infection and Genotypes in Patients with Hemophilia and Other Blood Coagulopathies in Mashhad, Iran

Background and Aim: Patients with blood coagulopathies treated with multiple transfusions have a high risk to acquire some viral infections such as hepatitis C. This research was aimed to identify hepatitis C virus (HCV) infection prevalence, and the viral genotypes among patients with hemophilia and other inherited coagulopathies in Mashhad, Iran. Methods: Medical records of 760 patients with inherited coagulopathies including hemophilia were reviewed in Sarvar Clinic of Mashhad. Plasma samples were subjected to detect antibodies against HCV (anti-HCV) by enzyme-linked immunosorbent assay. HCV RNA and genotypes were determined by a real-time polymerase chain reaction (PCR) method. Results: Totally 128 individuals (16.8%) including patients with hemophilia (n=116) and individuals with other coagulopathies (n=12) were found to be seropositive for anti-HCV. They comprised 122 men and six women with a mean age of 31.6 ± 10.5 years. The PCR results were available for 118 patients, of whom 86 individuals (72.9%) were found to have detectable HCV RNA in their serum. The most frequent genotypes were 1a and 3a (49.1% and 35.8%, respectively). HCV genotypes were not significantly correlated with the patients’ age (p=0.477) as well as with the serum levels of alanine aminotransferase (p=0.655) and aspartate aminotransferase (p=0.332). Conclusion: The patients with blood coagulation disorders had a greater prevalence of HCV infection in comparison with the general population in our region. The most common subgenotypes of HCV were 1a, and 3a, respectively. These results could assist professionals to choose more efficient approaches for the management of their patients. *Corresponding Author: Mohammad Reza Hedayati-Moghaddam; Email: drhedayati@acecr.ac.ir Please cite this article as: Badiei Z, Ahmadi-Ghezeldasht S, Sima HR, Habibi M, Khamooshi M, Azimi A, Hedayati-Moghaddam MR. The Prevalence of Hepatitis C Virus (HCV) Infection and Genotypes in Patients with Hemophilia and Other Blood Coagulopathies in Mashhad, Iran. Arch Med Lab Sci. 2021;7:1-7 (e9). https://doi.org/10.22037/amls.v7.33968

Abstract 807: Asian prevalent ABCB5 genetic variants rs2074000 and rs17143187 predicts overall survival and clinical outcomes in hepatocellular carcinoma patients

Abstract Background/Aims Incidence of HCC varies in diverse localities with differences on ethnicity and risk factors. The majority of HCC cases worldwide are from China, thus raising the concern on genetic susceptibility in addition to the prevalence of hepatitis virus infection. Drug transporter ABCB5 has been reported to be overexpressed in HCC and associated with poor survival. Recently a panel of SNPs and INDELs in ABCB5 gene have been reported to associate with HCC risk (Leung et al. 2020). We aim to further examine the ethnic differences on the ABCB5 genetic variations between local cohort and the data from The 1000 Genome Project. Subjects and Methods 300 HCC and 300 healthy blood samples were prospectively collected with informed consent. All patients had been diagnosed with primary HCC and underwent partial hepatectomy. Clinical information including sex, age, tumor stage and survival outcomes were collected prospectively. Genomic DNA were extracted from blood samples and SNPs were examined. SNP allele frequencies in different populations were obtained from The 1000 Genomes Browser by NCBI. Results Twelve ABCB5 genetic variants were within the coding regions, with one splicing variant, one stop codon change, while 2 were synonymous and 8 were non-synonymous changes. In particular, allele frequencies of rs2074000 observed in healthy local cohorts (C: 0.517 vs A: 0.483) were comparable to East Asian, while the genetic variation was absent in European in 1000 Genomes Project (CHB - C: 0.534 vs A: 0.466; CHS - C: 0.548 vs A: 0.452; GBR - C: 1.000 vs A: 0.000; CEU - C: 1.000 vs A: 0.000; P&amp;lt;0.001). Similarly, allele frequencies of rs17143187 in healthy local cohorts (G: 0.518 vs C: 0.482) were comparable to East Asian (CHB - G: 0.539 vs C: 0.461; CHS - G: 0.567 vs C: 0.433), while it was absent among European (GBR and CEU - G: 1.000 vs C: 0.000) (P&amp;lt;0.001). Data from our local HCC cohorts further demonstrated that rs2074000 and rs17143187 were independent protective factors in overall survival (Cox HR; rs2074000: 0.676, 95% CI: 0.49-0.93, P=0.017; rs17143187: 0.709, 95% CI: 0.51-0.98, P=0.038). These ABCB5 genetic variants were associated with early tumor stage (OR; rs2074000: 0.351, 95% CI: 0.21-0.59, P&amp;lt;0.001; rs17143187: 0.382, 95% CI: 0.22-0.65, P&amp;lt;0.001) and solitary tumor nodule (OR; rs2074000: 0.507, 95% CI: 0.30-0.86, P=0.012; rs17143187: 0.517, 95% CI: 0.30-0.88, P=0.015). Conclusions ABCB5 genetic variants rs2074000 and rs17143187 mainly prevalent in East Asian predicted better overall survival among HCC patients. ABCB5 is crucial in tumor-initiating cells in melanoma. ABCB5 rs2074000 (non-synonymous SNP, Gln to Lys, classified as damaging by SIFT score) and rs17143187 (splicing variant) both predicted to confer non-functional proteins, thus partly explain the protective effects. Further functional studies are warranted to comprehend the underlying mechanisms. Citation Format: Chun Philip Yeung, Ching Ning Charing Chong, Tan To Cheung, Kelvin Kwok Chai Ng, Paul Bo San Lai, Siu Tim Cheung. Asian prevalent ABCB5 genetic variants rs2074000 and rs17143187 predicts overall survival and clinical outcomes in hepatocellular carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 807.

Abstract 76: Global LINE-1 Hypomethylation as Novel Biomarker for Cervical Cancer in Nigerian Women Living with HIV

Abstract Purpose: Nigeria faces a high health burden of cervical cancer (CC), which is worsened by high prevalence of human immunodeficiency virus (HIV) infection. Repetitive elements (RE) are DNA sequences that occur in multiple copies throughout the human genome. HIV infection can lead to RE hypomethylation that causes genome instability, an event often seen in the early phase of tumorigenesis. We aim to examine global RE hypomethylation as a novel epigenetic biomarker for CC among HIV-positive women in Nigeria. Methods: This study involved three groups of women: a) HIV-positive with CC (n=39); b) HIV-positive and cancer-free (n=52); and c) HIV-negative with CC (n=23). We estimated three types of global RE methylation in cervical tissue using genome-wide methylation data: long interspersed nuclear elements (LINE-1), Alu, and human endogenous retrovirus (HERV). We used multiple linear regression adjusting for age, education, parity, employment, cancer stage, body mass index, and sample batch to compare the biomarkers across the HIV/ICC groups and paired t-test to compare 26 pairs of tumor vs. surrounding normal tissues, stratified by HIV status. Receiver operating characteristic curve (ROC) and area under the ROC (AUC) were used to examine the diagnostic value. Results: Among HIV-positive women, all 3 global RE methylation biomarkers were hypomethylated in CC compared to cancer-free (LINE-1: mean difference [MD]=-0.049, p-value=2.9e-8; Alu: MD=-0.011, p-value=2.0e-4; HERV: MD=-0.013, p-value=1.7e-6). Paired analyses showed a larger, more significant MD in HIV-positive stratum than HIV-negative, especially LINE-1 (MD=-0.048 vs. -0.020, p-value=0.004 vs. 0.254). LINE-1 achieved the highest AUC (0.85, 95% CI: 0.76-0.95) in distinguishing tumor tissue from normal tissue among HIV-positive women, followed by HERV (0.82, 95% CI: 0.73-0.92) and Alu (0.60, 95% CI: 0.47-0.72). Conclusion: Global LINE-1 hypomethylation may serve as a novel biomarker for CC screening and early detection for women living with HIV in low- and middle-income countries. Citation Format: Yinan Zheng, Jonah Musa, Kyeezu Kim, Yishu Qu, Brian Joyce, Jun Wang, Demirkan Gursel, Olugbenga Silas, Abdulkareem Fatimah, Godwin Imade, Alani Akanmu, Jian-Jun Wei, Masha Kocherginsky, Kwang-Youn Kim, Firas Wehbe, Chad Achenbach, Rose Anorlu, Melissa Simon, Atiene Sagay, Folasade Ogunsola, Robert Murphy, Lifang Hou. Global LINE-1 Hypomethylation as Novel Biomarker for Cervical Cancer in Nigerian Women Living with HIV [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 76.

Molecular and Serological Prevalence of HCMV in Iranian Patients with Breast Cancer.

Background:Human cytomegalovirus (HCMV) is prevalent viral infection involved in several human cancers including breast cancer. The presence of HCMV genome in breast cancer tissue and footprint of viral last exposure patient’s serum are considered as important factor in the process of breast cancer development. Objectives:This study aimed to investigate molecular and serological epidemiology of HCMV in patients with breast cancer in Iran for first time. Methods:In our case-control study, 98 samples of breast tissue, including 49 cancerous (case) and 49 adjacent non-cancerous tissue were collected (control). In addition, we collected sera samples from all patients (n=49) and healthy individual (n=49). Seroprevalence of HCMV was assessed by Enzyme-linked immunosorbent assay (ELISA) and detection of HCMV genome was performed using Nested-PCR method. Results:HCMV genome found in 16.3% (8/49) of cases tissue and 2% (1/49) of controls tissue. In patients group, the levels of anti-CMV IgG and IgM were 93.9% and 2% compared to 69.4% and 4.1% in healthy individuals, respectively. There was a statistically difference between the anti-CMV IgG in patients and healthy control (p= 0.002). We found 75% of (6/8) HCMV genome positive PCR samples were also positive for their anti-CMV IgG in cases which was statistically significant (p= 0.01). Conclusions:Our result showed significant presence of HCMV genome and anti-CMV IgG in patients, supporting the role of HCMV in breast cancer.