Detection of Major Human Herpesviruses in Iranian Patients with Suspected Encephalitis Using Multiplex Polymerase Chain Reaction.

BACKGROUND: The Herpesviridae family plays a significant etiological role in central nervous system viral infections during primary infection or reactivation from a latent form. Early detection is crucial because prescribing some antivirals can prevent severe side effects or life-threatening conditions. METHODS: In this study, 251 CSF specimens were collected from patients with clinical suspicion of viral encephalitis in Pars Hospital, Tehran, Iran. DNA was extracted, and a multiplex PCR was designed to investigate the presence of herpes simplex virus-1, herpes simplex virus-2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. RESULTS: Overall, 59 cases of the 251 CSF samples were positive for multiplex PCR (23.5%). The most frequent positive findings were EBV and HSV, with a prevalence of 10.3% and 8.7% (5.5% HSV-1 and 3.1% HSV-2), respectively. Four co-infections were also seen in this study. CONCLUSIONS: This multiplex PCR assay detects simultaneously different herpesviruses in CSF samples of patients with suspected encephalitis in 2 rounds of PCR amplification; therefore, it is a reliable and cost-saving diagnostic method for evaluating patients infected with herpesvirus with neurological disorders.

Detection of human papillomavirus genotypes, herpes simplex, varicella zoster and cytomegalovirus in breast cancer patients.

BACKGROUND: The role of viruses as a cause of breast cancer (BC) has been significantly investigated in recent years. Human papillomavirus (HPV) has been detected in invasive breast carcinomas, while most studies have only focused on the detection of viral DNA, we aimed to examine the prevalence and genotypes of HPV among Iranian BC patients. We also examined the presence of herpes simplex-1 (HSV-1), herpes simplex-2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) in these samples. METHODS: We collected and analyzed 70 Formalin-Fixed Paraffin-Embedded (FFPE) blocks including 59 BC samples, and 11 benign breast lesions as control from Iranian patients using nested PCR. Real-time PCR utilized as a confirming test to nested PCR findings. Genotyping of HPV positive samples was performed, the samples were also subjected to a multiplex PCR to detect HSV-1, HSV-2, VZV, and CMV in BC. RESULTS: Papillomavirus DNA was present in 7 of 59 BC samples (11.8%); while none was detected in control samples. The most prevalent type was HPV18, followed by HPV 6. All HPV positive patients had high tumor grades (II/ III) with a histologic diagnosis of ductal carcinoma. The patient age range was 33 to 73 years with a median of 51 years. Most of HPV positive patients had low levels of education. HPV16 was not detected. Also, 5 of 59 BC specimens (8.47%), were positive for HSV-1. But none of the samples were positive for HSV-2, VZV, and CMV. CONCLUSIONS: Our results suggest a carcinogenesis role for High-risk HPV (HPV18) in breast tumors. Our findings of HSV-1 and low-risk HPV (HPV6) in BCs may propose a cancer-causing role for them. Further large-scale studies are warranted to assess the significance of our findings.

Detection of HSV-1, HSV-2 and VZV Isolated from Cerebrospinal Fluid Samples of Children Suspected to Encephalitis.

Background: Encephalitis is an uncommon, serious brain infection that can cause fatality among children. The cause of most encephalitis remained unknown, yet viruses are the most well-known infectious agents that cause encephalitis. This study aimed to determine varicella-zoster virus (VZV) and herpes simplex virus type 1, 2 (HSV1/2) among individuals who are under 5 years of age in Iran. Materials and Methods: In this study, 149 cerebrospinal fluid samples of suspected patients of encephalitis were analyzed with some symptoms, such as seizure, fever, nausea loss of consciousness, and dizziness from Mofid Children's Hospital in Tehran, Iran. Then, the molecular evaluation of samples was performed using multiplex Polymerase Chain Reaction (PCR) for detecting HSV1/2 and VZV. Results: The mean age of the patients was 1.8 years. Also, 63.4% of children were male and 36.6% were female. Out of 149 tested samples, 11 (7.3%) showed the viral DNA for one of the herpes viruses (7.3%). Nine samples were HSV1 positive (6.0%) and two samples were VZV positive (1.3%). Fever and vomiting were the most frequent symptoms. The mean ± standard deviation (SD) WBC and counts in cerebrospinal fluid (CSF)-positive samples, and all included samples were 298.8 ± 552.7 cells/µL and 131.1 ± 474.6 cells/µL, respectively. Conclusions: Although viral encephalitis is considered a threat to children's health, with accurate diagnosis and appropriate antiviral drugs, death and neurological complications in children can be prevented.

The roles of programmed death ligand 1 in virus-associated cancers.

Programmed death ligand 1 (PD-L1) is a surface glycoprotein that induces T-cell anergy or apoptosis by binding to PD-1 on activated T and B cells. It is also known as a cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1). Suppressing the adaptive arm of the immune system is the critical role of PD-L1.so it prohibits the proliferation of activated T cells and reduces apoptosis in regulatory T cells. When PD-L1 binds to PD-1, it prevents T cells from killing other cells such as cancer cells. Viruses have various strategies to evade from the immune system such as modifying host gene expression or deregulating proteins function. So they can directly or indirectly change the expression of PD-L1. This study proposed to evaluate the effect of viruses on the expression of PD-L1 which leading to uncontrolled cell growth and tumor formation. We have studied serious tumorigenic viruses, including Human Papillomaviruses (HPV), Epstein-Barr viruses (EBV), Human T-cell leukemia viruses type 1 (HTLV-1), Hepatitis B viruses (HBV) and Hepatitis C viruses (HCV). So we surveyed the correlation between the presence of viruses and expression of PD-L1. Most studies showed the PD-L1 overexpression due to viral functions; however, further studies are needed to better understand the role of the PD-1/PD-L1 pathway in virus-associated cancers as a candidate of anti- PD-L1 therapy.

Prevalence of Epstein-Barr virus (EBV) in Iranian Breast Carcinoma Patients.

INTRODUCTION: Breast cancer (BC) is the most common malignancy affecting females worldwide. Various risk factors play a role in the developing of BC. Infectious agents like viruses have been proposed for this cancer and Epstein-Barr virus (EBV) is a widely researched candidate virus. This study detects the presence of EBV-DNA in breast cancer patients. METHODS: The study was conducted on 59 formalin-fixed paraffin-embedded (FFPE) tissue blocks samples of women with breast carcinoma and 11 non-neoplastic breast controls. The DNA was extracted for all the samples. Then detection of EBNA1 EBV was done by polymerase chain reaction (PCR). RESULTS: EBV was detected in 6.7% (4/59) of patients while all breast control samples were negative. All patients with positive EBV-DNA were high tumor grades (II, and III). Also, they had a low level of educations. CONCLUSIONS: According to our findings, it can be suggested that EBV may have a potential role in breast cancer development. However, this study provides substantial but not conclusive evidence for the involvement of viruses in BC disease development. Therefore, future investigations are needed to elucidate the exact role of EBV in breast cancer.
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