Добірка наукової літератури з теми "Hepatitis B; human haemopoietic cells"

Hepatitis B virus (HBV), an enveloped partially double-stranded DNA virus, is a widespread human pathogen responsible for more than 250 million chronic infections worldwide. Current therapeutic strategies cannot eradicate HBV due to the persistence of the viral genome in a special DNA structure (covalently closed circular DNA, cccDNA). The identification of sodium taurocholate co-transporting polypeptide (NTCP) as an entry receptor for both HBV and its satellite virus hepatitis delta virus (HDV) has led to great advances in our understanding of the life cycle of HBV, including the early steps of infection in particular. However, the mechanisms of HBV internalization and the host factors involved in this uptake remain unclear. Improvements in our understanding of HBV entry would facilitate the design of new therapeutic approaches targeting this stage and preventing the de novo infection of naïve hepatocytes. In this review, we provide an overview of current knowledge about the process of HBV internalization into cells.

Hronic hepatitis B belongs to a category of socially significant diseases due to its wide abundance in the world and high frequency of unfavourable outcomes of this disease. Features of interaction of hepatitis B virus with human immune system, accompanying development of mechanisms of escape from immunological control, is the basis of development of chronic hepatitis B. Molecular-biological features of hepatitis B virus are the basis of the indicated mechanisms, and the content of this review is their examination. Herewith, stages of immunopathogenesis of this disease is the basis of characteristics of interaction of viral proteins with cells of immune system, and isolation of those is accepted in contemporary foreign literature.

More than 350 million people worldwide are persistently infected with human heptatitis B virus (HBV) and at risk to develop liver cirrhosis and hepatocellular carcinoma making long-term treatment necessary. While a vaccine is available and new antiviral drugs are being developed, elimination of persistently infected cells is still a major issue. Recent efforts in adoptive cell therapy are experimentally exploring immunotherapeutic elimination of HBV-infected cells by means of a biological attack with genetically engineered “designer” T cells.

Tc17 cells and the semi-invariant human mucosal associated invariant T (MAIT) cells are important CD8+ tissue-homing cell populations. Both are characterized by high expression of CD161 (++) and type-17 differentiation, yet their origins and relationships remain poorly defined. By transcriptional and functional analyses it is demonstrated that a pool of polyclonal, pre-committed type-17 CD161++CD8αβ+ T cells exists in cord blood, from which a prominent MAIT cell (TCR Vα7.2+/Vβ2 or 13.2) population emerges post-natally. During this expansion, CD8αα T-cells appear exclusively within CD161++CD8+/MAIT subset, sharing cytokine production (IL17, IL-22 and IFN-γ), chemokine-receptor expression (CCR2, CCR6 and CXCR6), TCR-usage and transcriptional profiles with their CD161++CD8αβ+ counterparts. These data demonstrate the origin and differentiation pathway of MAIT cells from a naïve type-17 pre-committed CD161++CD8+ T cell pool and the distinct phenotype and function of CD8αα cells in man. The CD161++CD8αβ and CD8αα T cell subsets are reduced in the peripheral circulation in chronic hepatitis B and C and are enriched in the liver in chronic hepatitis C. Their potential role in immunity to chronic viral hepatitis B and C is demonstrated by their expression of activation/exhaustion markers CD69, CD25, HLA-DR and PD-1. In addition a substantial distinct CD161-CD8β^low population is demonstrated in chronic hepatitis B, co-characterised by a CD28^low, HLA-DR^high phenotype and high expression of IFN-γ, with important implications for the development of immunotherapy and vaccination.

Les lymphocytes T CD4 (LT CD4) jouent un rôle central dans la régulation des réponses immunitaires vis-à-vis des agents infectieux et des vaccins. Cependant, leur différenciation in vivo est encore mal comprise et les caractéristiques des LT CD4 capables de persister à long terme tout en assurant une réponse immunitaire protectrice sont mal définies. L’approfondissement de ces connaissances est indispensable pour le développement de nouveaux vaccins.

Pour approcher cette question, nous avons utilisé deux approches expérimentales. La première est un suivi de la différenciation des LT CD4 au cours de la réponse immune primaire chez des sujets vaccinés contre l’hépatite B ;la deuxième est la caractérisation phénotypique et fonctionnelle des LT CD4 mémoires antigène(Ag)-spécifiques pendant la phase d’état. Cette analyse a été réalisée au sein des LT CD4 spécifiques d’Ag vaccinaux, l’Ag de surface du virus de l’hépatite B (HBs) et la toxine tétanique (TT), ainsi que ceux spécifiques des Ag du cytomégalovirus (CMV). Les LT CD4 Ag-spécifiques ont été mis en évidence par cytométrie de flux après marquage intracytoplasmique du ligand du CD40 (CD40L) exprimé en réponse à une stimulation de courte durée par l’Ag. Des expériences basées sur la stimulation par la toxine du syndrome du choc toxique et le marquage du segment Vbeta2 du récepteur des LT ont démontré la bonne sensibilité et spécificité de cette méthode.

Le suivi de la réponse primaire chez 11 donneurs jusqu’à plus d’un an après immunisation par le vaccin anti-hépatite B a permis d’établir un modèle de différenciation des LT CD4 Ag-spécifiques in vivo chez l’homme. Nous avons mis en évidence des LT CD4 spécifiques d’un nombre limité de peptides immunodominants de la protéine HBs suggérant une réponse de type oligoclonale. Grâce à l’utilisation d’un cytomètre neuf couleurs, nous avons mené une analyse détaillée de l’hétérogénéité de la population mémoire HBs-spécifique. L’expression du CCR7 permet de distinguer des cellules de type mémoire centrale (LTCM, CCR7+) et effectrice (LTEM, CCR7-) se distinguant notamment par leur capacité à migrer vers les ganglions lymphatiques ainsi que par leurs propriétés fonctionnelles. Nous avons montré l’existence de ces deux sous-populations au sein des cellules HBs-spécifiques mais par opposition à leur définition initiale, ces LTCM sont capables de produire des cytokines effectrices. La proportion importante de LTCM exprimant le Ki67 témoigne d’une activité proliférative persistante in vivo et suggère la capacité de ces cellules à s’auto-renouveler et éventuellement à alimenter le pool des LTEM. La proportion importante de LTCM exprimant la chaîne alpha du récepteur à l’IL-7 (CD127) suggère que ces cellules sont sensibles aux signaux émanant de l’IL-7, une cytokine dont le rôle dans le maintien de la mémoire lymphocytaire T est connu. Compte tenu de la relevance potentielle de ces caractéristiques uniques pour le développement de vaccins et de l’accumulation de travaux montrant l’avantage sélectif des LTCM à conférer une immunité protectrice, nous avons focalisé la dernière partie de ces recherches sur cette sous-population. Une étude transversale des LTCM spécifiques de plusieurs types d’Ag (éliminés (HBs et TT) ou persistants (CMV)) a été menée. Nos résultats montrent une hétérogénéité, variable selon l’Ag, de la capacité de ces cellules à produire des cytokines effectrices et de leur phénotype de différenciation. Cette donnée nouvelle soulève la possibilité que les LTCM soient hétérogènes dans leur capacité à conférer une immunité protectrice. L’acquisition du marqueur KLRG1 par une fraction des LTCM s’associe à une capacité accrue à produire des cytokines effectrices et à une expression élevée du CD127. La possibilité que ces cellules soient particulièrement aptes à conférer une immunité protectrice et durable est discutée, tout comme les mécanismes menant à leur génération et l’intérêt de ces connaissances pour la conception de nouveaux vaccins.

Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished

This thesis studied aspects of the interaction of hepatitis B virus (HBV) with haemopoietic cells and cell lines, to address the reported tropism of HBV for haemopoietic tissues. Emphasis was directed at demonstrating specific attachment of HBV to defined subpopulations of peripheral blood leucocytes (PBL) and bone marrow cells (BM), and the distribution of receptors for HBV on well-defined haemopoietic cell lines. Biochemical characterisation of the virus-cell interaction was also performed, and the question of infectivity of haemopoietic cell lines was addressed' Firstly, a quantitative assay of HBV binding to liver plasma membranes (PM) was adapted to show that isolated PBL PM bound serum-derived FIBV particles to a similar degree, based on their protein content. Using synthetic peptides representative of various amino acid sequences of the preSl and preS2 regions of L HBsAg to inhibit HBV binding to the pM, it was found that peptide pres l(12-32) inhibited binding to PBL PM by 60-80% and peptide preSl(21-47) inhibitedby 0-30% (depending on the source of PM), while peptides preSl(32-49) and preS2(120-145) did not inhibit binding. This contrasts with results obtained using liverPM, where peptide preSl(12-32) did not inhibit binding, while peptide preSl(21- 47) inhibited by 70%, and preSl(32-49) inhibited by approximately 12%. Peptide preS2(120- 145) had no effect on binding. Thus, different regions of the L surface protein appear to mediate attachment to PBL and hepatocytes. HBV particles isolated from serum are complexed with serum proteins including IgG. To test the involvement of receptors for IgG and complement fragments (opsonins) in the HBV-PM interaction, a panel of ligand-blocking monoclonal antibodies (MAbs) to opsonin receptors was used, and it was shown that the three classes of receptors for IgG (FcγRI, FcγRII and FcγRIII) and CR3, are not major receptors for HBV on PBL or hepatocytes, as MAbs to these did not inhibit HBV binding. It was also shown that HBV does not utilise the receptor for IgA, FcαR, for attachment to PBL, despite reported sequence homology between the large envelope protein of HBV and the Fc portion of human IgA. In contrast to a published report that IL-6 mediates binding of HBV to hepatocytes, IL-6 was shown not to mediate attachment to either liver or PBL PM, by virtue of pre-incubation with a blocking polyclonal anti-serum to IL-6. Glycosaminoglycans (GAGs) were found to influence HBV binding to PM: soluble heparin (HE) inhibited binding to liver PM by up to 80%, and to leucocyte PM by up to 40%; chondroitin sulphare C (CS-C) enhanced virus binding (approximately 1.5-fold) to leucocyte pM only. Chondroitin sulphate A and hyaluronate had no effect on binding to either PM, arguing that simple electrostatic properties of GAGs were not responsible for the observed effecrs. The incomplete inhibition by HE and enhancement by CS-C could indicate the presence of more than one class of binding site for HBV on the respective PM, and coupled with the differential pattern of inhibition in the presence of synthetic peptides, argues that receptors for HBV on pBL and hepatocytes may be either different, or altered forms of the same molecule(s). To extend these studies, whole cell binding assays were developed in order to accurately define which subsets of pBL and BM cells could bind HBV. Using purified HBV particles as the first stage in an immunofluorescence-based detection system, followed by detection of bound HBV using anti-preS1 MAbs F35.25 or MAl8/7, and a FlTC-conjugated third-stage antibody, specific membrane staining of peripheral blood monocytes from 8/9 donors was observed. In addition, binding of HBV to the erythroleukaemia cell line K562 was observed, while other myeloid cell lines did not appear to bind virus. This assay was then adapted to a suspension cell assay with analysis by flow cytometry, using phycoerythrin as the detecting fluorochrome. The parameters of binding were optimised for K562 cells and these were then applied to analyse HBV binding to PBL and BM cells obtained from healthy volunteers, whose serum was free of HBV markers. Based on their light scattel characteristics, monocytes and neutrophils were the only cell types in the peripheral blood that bound HBV' while binding to lymphocytes was not observed. This was confirmed by two-colour immunofluorescence to simultaneously detect bound HBV and subset-specific leucocyte markers. Similarly, in the BM, only monocytes bound HBV. Importantly, haemopoietic stem cells (cD34+) did not bind HBV. Binding was tested to 'activated' populations of lymphocytes (pHA-treated), monocytes (LPS-treated), and neutrophils (fMLP-treated). The pattern of HBV binding was not affected by these treatments. Monocytes cultured in vitro, bound significantly more virus than freshly isolated monocytes. Taken together, these results indicate that only monocytes, and to a lesser extent neutrophils, express potential receptors for HBV, and a differentiation-dependent upregulation of receptor sites for HBV is observed on Monocytes The distribution of potential HBV receptors was determined on a number of haemopoietic cell lines, representative of various haemopoietic lineages. K562 (erythroid), and the monocyte cell line THP-l, were the only haemopoietic cell lines which bound HBV, while binding was also observed to the human hepatoma cell line HepG2. A number of other erythroid and monocyte cell lines, as well as T and B tymphoid, and a megakaryocytic line, all failed to bind HBv. A comparison of the surface immunophenotypes of all the cell lines tested excluded all known CD-classified molecules (including opsonin receptors), as candidate HBV receptors. The biochemical characteristics of the interaction of HBV with all of these cell types were then examined. On K562 and THP-1, HBV binding was sensitive to the protease chymopapain but insensitive to trypsin, indicating that the molecule was a glycosylated protein. Pre-treatment of these cell lines with tunicamycin, to inhibit post-translational addition of N-linked carbohydrate to surface glycoproteins, did not influence HBV binding, indicating that these moieties are not important for virus attachment. Enzymatic removal of cell surface sialic acids with neuraminidase significantly enhanced HBV binding to K562 and THP-1 cells but did not confer binding to otherwise 'negative' cell lines. Binding of HBV to cultured monocytes and HepG2 cells was trypsin and chymopapain sensitive' and was not increased by neuraminidase pre-treatment. Cation chelation demonstrated that HBV binding of to all cell types was Ca²⁺/Mg²⁺-independent, and acid elution of cells showed that binding was not mediated by peripherally-bound molecules. Binding of HBV to monocytes and to HepG2 cells was significantly reduced by pre-treatment of the cells with PI-PLC, implying that the molecule responsible for binding to these cells is GPl-linked. In this case, a comparison with HBV binding to K562 was not informative due to the resistance of the GPI linkages on these cells, and possibly also on THP-I cells (based on CD59 cleavage), to hydrolysis by PI-PLC. Thus, cells expressing potential receptor(s) for HBV, whose characteristics do not correlate with any other proposed candidate, have been identified. Immunoprecipitation analysis using HBV particles covalently cross-linked to the surface of ¹²⁵I-labelled K562 cells, and anti-S MAb coupled to goat anti-mouse IgG-Sepharose, resulted in the identification of a 50 kDa species as a putative HBV receptor. Contrary to reports that HBV inhibits colony formation by myeloid cell lines in semi-solid media, no inhibitory effect by HBV was seen on clonal cell growth in liquid culture. K562 cells were found to be able to efficiently internalise HBV particles, which accumulated in a perinuclear compartment. In infection studies, K562 cells positive for HBsAg aftet 2-4 days post-infection became enlarged, and their numbers decreased steadily over an 11 day period. It is not clear whether these cells represent a transient or differentiated cell type. Similarly, it appears that the level of HBV DNA in these cells declines steadily during the infection course.
Thesis (Ph.D.) -- University of Adelaide, Dept. of Microbiology and Immunology, 1998

碩士
國立陽明大學
生物化學研究所
89
Abstract HE-145 has been shown to suppress HBsAg production and stimulate cell proliferation on human hepatoma Hep3B/T2 cells. Similarly, TPA and insulin suppress HBsAg and stimulate cell growth. In this study, we investigated the effects of HE-145, TPA and insulin on the activities of human protein promoter in Hep3B/T2 cells, while suppressing the HBsAg production. At the same time, the HBV gene expression and replication of HepES2 cells were examined to identify the effect of HE-145, TPA, and insulin on HBV genome. HE-145, TPA and insulin suppressed HBsAg production in a does — dependent manner on Hep3B/T2 cells. The promoter activities were assayed by transient transfection with various plasmids, containing either the promoter region of HBV or human proteins with a reporter gene of luciferase, into the Hep3B/T2 cells. HE-145, TPA and insulin were found to suppress SPII luciferase and CP luciferase activity in a dose-dependent manner on Hep3B/T2 cells. This suggested that the HBsAg production might mediate SPII promoter. Addition of 1.5 M HE-145 increased cyclin A promoter activity three folds while addition of TPA and insulin had no effect. This suggested that the growth stimulatory effect was due to activate cyclin A promoter at the transcription level. HE-145 was also shown to suppress the promoter activity of CRE and NFB in a does — dependent manner. The NFB promoter activity was increased by 16 folds when treated with 200 nM TPA. At the same time, the stimulated promoter activity was decreased to four times higher than control under the combination treatment of TPA and HE-145. This result showed HE-145 down-regulation of NFB promoter activity. Northern blotting analysis was performed on HBV RNA transcripts. There are three major transcripts of approximately 3.5, 2.4, and 2.1 kilo-bases in the total cellular RNA extract on human hepatoma HepES2, Hep3B/T2, and HepG2/A2 cells. The HBV-specific transcripts were reduced among 3.0M HE-145, 200nM TPA, and 100 nM insulin treatment. This result corresponds to previous experiments using SPII and core promoter assay. A rational approach to the development of drugs for the treatment of HBV infection is to identify the compounds that specifically inhibit HBV DNA extracted from HepES2 cells exposed to 3.0M HE-145, 200nM TPA, and 100 nM insulin. The decrease in HBV DNA replication by HE-145 and TPA shows their potential to be an anti-HBV agent. The evidences revealed in this mechanism-based study may provide us with a clue to possible approaches for drug development in the future.

碩士
國立陽明大學
生化暨分子生物研究所
101
Hepatitis B virus (HBV) infection has been documented to associate with diabetes and hepatocellular carcinoma. The prevalence of HBV is common, especially in Asia. The aim of the study is screening Chinese herb medicine to identify agents which can suppress gluconeogenesis, enhancing hepatitis B viral gene expression and further to understand the signaling pathway. Firstly, the combination of 8-bromo-cAMP (cAMP) and dexamethasone (DEX) was used to mimic the fasting and stress condition in Hep3B/T2 cells. It has been found a synergistic effect on the induction of HBV core promoter activity and the key enzymes of gluconeogenesis: phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase) and peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α) mRNA and protein expression of PGC-1α using quantitative real-time PCR and Western Blotting respectively. It was found that Chinese herb Duzhong (Eucommia ulmoides) and one of its active flavonoid components, Quercetin dose-dependently suppressed G6Pase, PEPCK and PGC-1α mRNA; protein expression of PGC-1α and HBV core promoter together identifying nt1656-1675 as binding sequences of core promoter. This identified nt1656-1675 as a response element in the HBV core promoter using serial deletion as well as point mutation at different regions of the core promoter. In addition, the overexpression of PGC-1α reversed the core promoter activity by Duzhong and Quercetin. To examine which intracellular signaling pathway is crucial for Duzhong and Quercetin, it had been seen that PI3K inhibitor wortmannin blocked AKT activation induced by Duzhong and Quercetin and abolished suppressive activity of Duzhong and Quercetin on cAMP/DEX activated HBV core promoter activity and gluconeogenetic enzyme expression. Therefore, it is proposed that Duzhong and Quercetin inhibit core promoter and gluconeogenic gene expression via activation of PI3K and AKT pathway. Finally, the Duzhong and Quercetin treatment significantly reduced HBV mRNA expression and core protein in 1.3ES2 cells. Overall, Chinese herb Duzhong and Quercetin may inhibit HBV gene expression through phosphorylation of AKT to down-regulate the host gluconeogenesis. This study which HBV is controlled by the hepatic metabolic gluconeogenesis may be the references of new drug developing of anti-HBV agents. The coming out rule of the close link between HBV and liver metabolism can be further exploited for host-targeted therapeutic strategies.

碩士
國立陽明大學
生化暨分子生物研究所
97
Hepatitis B virus (HBV) infection causes acute and chronic hepatitis, and the affected patients have an increased risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). Although a preventive vaccine for HBV is available, effective drugs to eradicate HBV in chronic carriers are still urgently needed.The Chinese herbal medicine Xiao-Chai-Hu-Tang consists of Bupleuri radix and Scutellaria radix (HD-1S) and is widely used for treatment of liver disease. In searching of compounds on suppression of hepatitis B surface antigen (HBsAg) production, our laboratory previously have shown that HD-1S strongly suppressed hepatitis B surface antigen (HBsAg) in human hepatoma cells. In this study, I demonstrated that the aqueous extract of HD-1S and one of its components Wogonin had potent anti-HBV activity. Both HD-1S and Wogonin not only suppressed HBsAg production but also decreased HBV transcripts and HBV viral particles in cultured human hepatoma cells. To understand the molecular mechanism of suppression of HBV gene expression by HD-1S and Wogonin, the effects of HD-1S and Wogonin on four viral promoter activities using luciferase as a reporter were examined. This study showed clearly that both HD-1S and Wogonin selectively suppresses core promoter (CP) of HBV. Such suppressive effects of HD-1S and Wogonin are liver-specific because no suppressive activity of HD-1S and Wogonin was observed when CP activity was assayed in non-liver 293T cells. Furthermore, ectopic expression of PGC-1�� and PPARr/CEBP�� abolished the suppressive effect of HD-1S and Wogonin on HBV CP activity, respectively. Therefore, HD-1S and Wogonin may selectively modulate transcriptional machinery of human liver cells to suppress HBV gene expression and replication. Results from this study also suggested that some components other than Wogonin might also have novel anti-HBV activity and deserve futher investigation in the future.

碩士
國立陽明大學
生物化學研究所
87
HE-145 was isolated from the heartwood of the stem of Taiwania cryptomerioides Hayata. HE-145 suppressed endogenous HBsAg production in long-term cultured human hepatoma Hep3B/T2 cells, but has no cytotoxicity on the cells. HE-145 suppressed the HBsAg production on Hep3B/T2 cells in a dose-dependent manner with IC50 of 56 nM for short-term culture. Previously Northern blotting analysis showed that the suppression of HBsAg gene expression by HE-145 were mainly at the m-RNA level. So, it is interested to know the effect of HE-145 on the promoter activity of HBV genome in Hep3B/T2 cells. In these studies, we investigate the promoter activity of HBV genome in human hepatoma cells Hep3B/T2, and HuH-7. Human hepatoma Hep3B/T2 cells carry an integrated HBV genome in its chromosome, and continuous secretion of HBsAg into culture medium. Human hepatoma cells, Huh-7, carry no endogenous HBV genome. The promoter activity assay was performed after transient transfection with various plasmids that contains promoter region of CAT with the HBV genome into Hep3B/T2, and HuH-7 cells. HE-145 suppressed SPII promoter, but stimulated core promoter on Hep3B/T2, and HuH-7 cells both in a dose-dependent manner. In contrast to the promoter activities of SPI and X do not show dramatically different by HE-145 concentration up to 2.8 μM. Additionally, HE-145 not only stimulated human protein cyclin A promoter activity, but also dominantly suppressed SPII promoter in Dexamethasone-treated cells. It reported that the suppression of HBsAg production by insulin mediated through PI3-Kinase. In order to observe the effect of suppression of HBsAg production by HE-145, the PI3-Kinase inhibitor wortmanin was used in human hepatoma Hep3B/T2 cells. The result suggests that PI-3 kinase may involve the suppression mechanism of HBsAg production by HE-145 in Hep3B/T2 cells. In this thesis, these results can be used to the further investigative approaches for the regulatory mechanism of HE-145 in human hepatoma cells in the future.

碩士
東海大學
生物學系
91
Hepatocellular carcinoma (HCC) is one of the ten major leading death diseases in Taiwan. The causal agent of HCC is hepatitis B virus (HBV) which encodes a protein (HBx). X gene is the smallest open reading frame (ORF) among hepatitis B virus (HBV) genome and it encodes the HBV X protein (HBx). The HBx is a multifunctional protein that is implicated in the pathogenesis of hepatocellular carcinoma. Very little is known about its functional mechanisms although interactions with several nuclear and cytoplasmic proteins have been demonstrated in vitro, there is no clear consensus as to the location of HBx in infected hepatocytes. So quantification and cellular distribution of the hepatitis B virus X protein in human hepatocellular carcinoma were studied. Western immunodetection of HBx antigen in liver extracts of twenty HCC patients was performed using the anti-HBx monoclonal antibody. The results show that 85% liver tissues of HCC contain a specific and comigrated HBx antigen. To further elucidate the role of HBx, the distribution of HBx was also examined by immunohistochemical staining. Eight fresh liver tissue samples, normal and tumor parts of four HCC patients were analysed. HBx was detected in both normal and tumor tissues using anti-HBx monoclonal and polyclonal antibodies. HBx was mainly located in cytoplasm. This distribution analysis of HBx will provide the basis for the study of the functional identification of the HBx.

This chapter reviews the current recommendations for adult persons living with HIV (PLWH) in the United States regarding vaccine-preventable diseases. In clinical practice, PLWH should be offered annual influenza vaccine; a combination of tetanus, diphtheria, and pertussis vaccine; depending on previous vaccination, pneumococcal vaccine, meningococcal conjugate vaccine, and hepatitis A and hepatitis B vaccines. Human papilloma virus vaccine can be given in PLWH up until the age of 26. Live vaccines, including the measles-mumps-rubella vaccine and varicella vaccine, can be given in those individuals who have CD4 cell counts of greater than 200 cells/mm³ and did not receive these vaccines during childhood. Some expert panels endorse recombinant zoster vaccination in PLWH at least 50 years old, although there is no current official recommendation from the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. The chapter covers routine vaccinations for PLWH.

Viruses are important in cancer for three main reasons: as a cause of cancer—about 15% of the worldwide cancer burden is due to viruses; in understanding of the biology of cancer-through the discovery and characterization of oncogenes and tumour suppressor genes; and in the treatment of cancer—some viruses selectively replicate in and destroy proliferating cells, viruses as foreign antigens may aid the recognition of cancer cells by the host’s immune system (‘xenogenization’), and viruses can also be used as vectors for immunization and for gene therapy. Viral cancers are prevented by early screening for tumours, screening for the virus in order to prevent transmission, and immunization as in the cases of hepatitis B virus and human papilloma virus.

Viruses are important in cancer for three main reasons: (1) As a cause of cancer—about 15% of the worldwide cancer burden is due to viruses: retroviruses can activate cellular oncogenes; (2) In understanding of the biology of cancer—through the discovery and characterization of oncogenes and tumour-suppressor genes. (3) In the treatment of cancer—some viruses selectively replicate in and destroy proliferating cells, viruses as foreign antigens may aid the recognition of cancer cells by the host’s immune system (‘xenogenization’), and viruses can also be used as vectors for immunization and for gene therapy. Viral cancers are prevented by early screening for tumours, screening for the virus in order to prevent transmission, and immunization as in the cases of hepatitis B virus (HBV) and human papilloma virus (HPV)...

This chapter addresses cancer viruses. A cancer arises from a single cell in the body multiplying unchecked until it has produced a whole mass of identical cells—a tumour. This can happen in any organ of the body, in people of any age, and in any country. The chapter begins by tracing the history of tumour virus discovery, particularly the discovery of the Epstein–Barr Virus (EBV). Clearly, the evolution of a virus-associated tumour is more complex than the simple equation ‘virus infection equals cancer’. Several other factors are involved in driving just one among many virus-infected cells to tumour growth. To investigate what these factors might be, the chapter then looks at how normal cell growth and division is regulated. It is no surprise to find that tumours caused by viruses are more common in people whose immune system is suppressed than in the general population. Ultimately, the easiest way to prevent infection and tumour development is with a vaccine, and this has been particularly successful with hepatitis B virus (HBV) and human papilloma virus (HPV). For those tumour viruses for which no vaccine is yet available, antiviral drug treatments are being used with some success.

Between 20 and 30% of human cancers are caused by infectious agents. These can be multicellular parasites, bacteria, or viruses. Whereas bacteria and parasites cause cancer by indirect mechanisms, such as inflammation and immune deregulation, viruses infect human cells directly and initiate molecular changes that lead to uncontrolled proliferation. Both DNA and RNA viruses, such as retroviruses, can cause cancer; however, the ability to promote cancer is a by-product of viral evolution and a low frequency event, often the result of faulty virus replication. Most human oncogenes, such as MYC, SRC, RAS, were first discovered because they had been pirated by retroviruses. The function of key human tumour suppressor proteins, such as RB and TP53, were identified because they bind to and are inactivated by DNA tumour viruses. Because viruses are foreign, vaccines can be devised that target them. More recently it has become possible to prevent two types of cancer caused by viruses—cervical cancer caused by human papillomavirus (HPV) and hepatocarcinoma caused by hepatitis B virus (HBV)—by preventing the initial infection using vaccination. Study of the relationship between infective agents and cancer has therefore achieved two main goals: to unravel basic mechanisms of carcinogenesis and to make some cancers preventable.