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      Association of Human Cytomegalovirus with Hodgkin’s Disease and Non-Hodgkin’s lymphomas

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          Abstract

          Background and Objective:

          The human cytomegalovirus (HCMV) can persist lifelong as a latent infection and may result in a series of disorders. Associations with both Hodgkin’s disease and non-Hodgkin´s lymphomas have been reported. Expression of the unique long (UL)138 gene of HCMV is linked with the viral latency phase while that of the immediate-early (IE)1 gene is typical of the viral replication phase in patients. This study conducted to determine the prevalence of CMV latent infection in histological tissue samples from patients with Hodgkin’s and Non-Hodgkin´s lymphomas.

          Material and Methods:

          A cross sectional study was carried out with a total of 50 paraffin embedded tissues blocks, including 25 samples for Hodgkin’s disease and 25 samples for non-Hodgkin´s lymphomas. After RNA extraction and cDNA preparation, detection of IE1 mRNA was conducted by RT-PCR and identification of mRNA UL138 was achieved by nested PCR.

          Results:

          Among 25 cases of Non-Hodgkin´s lymphoma, 5 (20%) were positive for UL 138 and 1 (4%) for both IE1 and UL 138. Among 25 cases of Hodgkin only 1 (4%) was positive for UL 138 and all were negative for IE1

          Conclusion:

          A relatively high 20% rate of expression of UL 138 was detected in patients with non-Hodgkin´s lymphoma, so that latent CMV infection may play a role in development of the disease.

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          Most cited references28

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          Human cytomegalovirus sequences expressed in latently infected individuals promote a latent infection in vitro.

          Latency enables human cytomegalovirus (HCMV) to persist in the hematopoietic cells of infected individuals indefinitely and prevents clearance of the pathogen. Despite its critical importance to the viral infectious cycle, viral mechanisms that contribute to latency have not been identified. We compared the ability of low-passage clinical and laboratory-adapted strains of HCMV to establish a latent infection in primary human CD34(+) cells. The low-passage strains, Toledo and FIX, established an infection with the hallmarks of latency, whereas the laboratory strains, AD169 and Towne, replicated producing progeny virus. We hypothesized that ULb' region of the genome, which is unique to low-passage strains, may encode a latency-promoting activity. We created and analyzed recombinant viruses lacking segments or individual open reading frames (ORFs) in the ULb' region. One 5-kb segment, and more specifically the UL138 ORF, was required for HCMV to establish and/or maintain a latent infection in hematopoietic progenitor cells infected in vitro. This is the first functional demonstration of a virus-coded sequence required for HCMV latency. Importantly, UL138 RNA was expressed in CD34(+) cells and monocytes from HCMV-seropositive, healthy individuals. UL138 might be a target for antivirals against latent virus.
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            Systematic review of the birth prevalence of congenital cytomegalovirus infection in developing countries.

            Congenital cytomegalovirus (CMV) infection is the leading infectious cause of congenital hearing loss and neurodevelopmental disability in developed countries. Information on congenital CMV infection in developing countries appears to be lacking. We conducted a systematic literature review to identify studies from developing countries with population-based samples of at least 300 infants that used laboratory methods established as reliable for the diagnosis of congenital CMV infection. Most studies were excluded due to biased samples or inadequate diagnostic methods; consequently the search identified just 11 studies that were from Africa, Asia, and Latin America. The number of newborns tested ranged from 317 to 12 195. Maternal CMV seroprevalence ranged from 84% to 100%. CMV birth prevalence varied from 0.6% to 6.1%. CMV-associated impairments were not documented in most studies. Birth prevalence ranges were higher than for Europe and North America, as expected based on the higher maternal CMV seroprevalence. With very limited data available on sequelae, the disease burden of congenital CMV in developing countries remains largely unknown at this time. Published by Elsevier Ltd.
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              Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study.

              Hepatitis B virus (HBV) infection is common throughout Asia and Africa. Whether chronic HBV infection increases risk of non-Hodgkin lymphoma (NHL) is unclear. We aimed to assess the association between chronic HBV infection and subsequent development of NHL in a South Korean cohort. The Korean Cancer Prevention Study is a cohort study of South Korean workers and their dependants enrolled during 1992-95. From this cohort, we excluded individuals who died before Jan 1, 1993, who had cancer at or before the initial visit, who had missing information about weight, height, alanine aminotransferase or aspartate aminotransferase concentrations, or alcohol use, or who had evidence of HIV or HCV infection. Of 1,284,586 eligible participants, 603,585 had baseline data for serum hepatitis B surface antigen (HBsAg) status and were included in our study. We regarded HBsAg positivity at baseline as evidence of chronic HBV infection. Participants were followed up from baseline until Dec 31, 2006. We used national databases of inpatient and outpatient diagnoses and mortality records to ascertain occurrence of haematological malignancies. We assessed incidence of NHL overall and of NHL subtypes, malignant immunoproliferation, Hodgkin's lymphoma, multiple myeloma, and various leukaemias. We used Cox regression to evaluate associations with HBsAg status, adjusting for sex, age, and enrolment year. 53,045 (9%) of 603,585 participants tested positive for HBsAg at baseline. Subsequently, 133 HBsAg-positive and 905 HBsAg-negative individuals developed NHL. HBsAg-positive participants had an increased risk of NHL overall compared with those who were HBsAg-negative (incidence 19.4 vs 12.3 per 100,000 person-years; hazard ratio [HR] 1.74, 95% CI 1.45-2.09, adjusted for sex, age at baseline, and enrolment year). Among NHL subtypes, HBsAg positivity was associated with increased risk of diffuse large B-cell lymphoma (n=325, incidence 6.86 vs 3.79 per 100,000 person-years; adjusted HR 2.01, 1.48-2.75) and other or unknown subtypes (n=591, incidence 10.5 vs 7.07 per 100,000 person-years; adjusted HR 1.65, 1.29-2.11), compared with HBsAg negativity. Increased risk was also recorded for malignant immunoproliferation (n=14, incidence 0.44 vs 0.15 per 100,000 person-years; adjusted HR 3.79, 1.05-13.7). Risk of these malignancies was consistently raised in HBsAg-positive participants throughout 14 years of follow-up. HBsAg positivity was not associated with follicular or T-cell NHL, Hodgkin's lymphoma, multiple myeloma, or various leukaemias. During extended follow-up, HBsAg-positive individuals had an increased risk of NHL, suggesting that chronic HBV infection promotes lymphomagenesis. Korean Seoul City Research and the National Research and Development Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea; US National Cancer Institute. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Asian Pac J Cancer Prev
                Asian Pac. J. Cancer Prev
                Asian Pacific Journal of Cancer Prevention : APJCP
                West Asia Organization for Cancer Prevention (Iran )
                1513-7368
                2476-762X
                2017
                : 18
                : 3
                : 593-597
                Affiliations
                [1 ] Health Research Institute, Infectious and Tropical Diseases Research Center, Ahvaz, Iran
                [2 ] Virology Department, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                [3 ] Pathology department, Imamkhomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                Author notes
                Article
                APJCP-18-593
                10.22034/APJCP.2017.18.3.593
                5464470
                28440608
                3f47feab-fa05-42fe-bca4-37f999522da8
                Copyright: © Asian Pacific Journal of Cancer Prevention

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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                Categories
                Research Article

                human cytomegalovirus,nested pcr,hodgkin disease,non-hodgkin lymphoma

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