The Relationship of the Virus to Nasopharyngeal Carcinoma

Klein, George

doi:10.1007/978-3-642-67236-1_15

Cited by 125 publications

(69 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is now both serological and cellular evidence (Anderson-Anvret et al, 1978;Klein, 1979;Saemundsen et al, 1982) in support of the association reported by Old et al (1966) (Klein, 1979).…”

supporting

confidence: 59%

Space-time clustering of nasopharyngeal carcinoma in Greenland Eskimos

Albeck¹,

Coleman²,

Nielsen³

et al. 1985

Br J Cancer

View full text Add to dashboard Cite

supporting

confidence: 59%

Space-time clustering of nasopharyngeal carcinoma in Greenland Eskimos

Albeck¹,

Coleman²,

Nielsen³

et al. 1985

Br J Cancer

View full text Add to dashboard Cite

“…The most abundant virus-encoded RNA species in LCLs, however, are small non-polyadenylated nuclear RNAs (EBERs) which are not translated into proteins (Howe & Steitz, 1986;Sample & Kieff, 1990). Other examples of latent EBV infection are provided by endemic Burkitt's lymphoma (BL) and undifferentiated nasopharyngeal carcinoma (NPC) (Epstein & Achong, 1979;Klein, 1979) the expression of latent viral antigens in these lesions is restricted to EBNA 1 in BL (Rowe et al, 1987a) and to EBNA 1 usually accompanied by LMP in NPCs (Young et al, 1988;Fahraeus et al 1988). In addition, the EBERs are transcribed in both BL and NPC, apparently to similar levels as in LCLs (Howe & Steitz, 1986;Rowe et al, 1987a;Gilligan et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

“…This was first apparent from the virus' association with undifferentiated NPC (Klein, 1979), but subsequently EBV has been observed replicating in normal oropharyngeal epithelial cells as these are shed into buccal fluid during the terminal stages of their differentiation (Lemon et al, 1977;Sixbey et al, 1984). This raises the possibility that EBV actually persists in the epithelial compartment and that virus replication at this site is responsible for continual secondary infection of the circulating B lymphocyte pool (Rickinson et al, 1985;Allday & Crawford, 1988).…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus Infection in Oral Hairy Leukoplakia: Virus Replication in the Absence of a Detectable Latent Phase

Niedobitek

Young

Lau

et al. 1991

Journal of General Virology

166

102

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) infects both B lymphocytes and oropharyngeal epithelium, and it has been argued that the true reservoir of virus persistence in vivo is the self-renewing basal epithelial compartment. The identification of oral hairy leukoplakia (HL) of AIDS patients as a clinically apparent focus of EBV replication in lingual epithelium therefore provides a means of studying the EBV-epithelial cell interaction in situ. Replicative EBV DNA and productive cycle antigens are restricted to the upper, more differentiated epithelial layers in HL, and here we have applied highly sensitive in situ hybridization and immunohistological methods to examine the lower basal/suprabasal layers for evidence of latent EBV infection. We could not detect EBV DNA in these layers using an in situ DNA hybridization protocol which, on reference B cell lines, detected 1 viral genome/cell. Likewise, using sensitive in situ RNA hybridization for both the small non-polyadenylated EBER RNAs (abundant transcripts seen in all known forms of EBV latency) and the latent membrane protein (LMP) mRNA (the most abundant viral mRNA in B lymphoblastoid cell lines), the basal/suprabasal cells in HL were consistently negative; immunohistological staining with specific monoclonal antibodies also gave no evidence of latently infected LMP-positive cells. When the biopsy extracts were analysed by immunoblotting with selected human antisera, in addition to abundant productive cycle antigens, a band of constant size (66K) was observed which also reacted with immunopurified antibodies monospecific for one of the latency-associated nuclear antigens, EBNA l; the cellular origin of this EBNA 1 could not be ascertained, but it is possible that in HL the protein is expressed during the productive cycle. The absence of demonstrable EBV latency in the basal/ suprabasal cells of HL suggests that this is purely a virus replicative lesion which is sustained by continual re-infection of the maturing epithelium, not by the maturation of latently infected cells from the basal compartment. IntroductionEpstein-Barr virus (EBV) is a human herpesvirus infecting more than 90~ of the population world-wide and persisting for life in the infected host. The best characterized target cell for EBV infection both in vivo and in vitro is the B lymphocyte; thus, when peripheral blood lymphocytes from virus carriers are placed in culture, EBV-immortalized B lymphoblastoid cell lines (LCLs) can be established by spontaneous outgrowth (Pope, 1967;Nilsson et al., 1971). Similarly, immortalization of B lymphocytes from previously uninfected individuals can be achieved by experimental EBV infection in vitro. Although a small subset of cells in LCLs may sustain EBV replication, the vast majority of cells remains non-productively (i.e. latently) infected. These latently infected B cells constitutively express a subset of viral genes encoding six EBV-encoded nuclear antigens (EBNA 1, 2, 3a, 3b, 3c and LP) and two membrane proteins, latent membrane protein (LMP) and terminal protein or ...

show abstract

“…Epstein-Barr (EB) virus is associated with widespread inapparent infection in man and is the cause of infectious mononucleosis (Henle & Henle, 1979); it is also strongly implicated in the aetiology of two human neoplasias, Burkitt's lymphoma (BL) (Epstein & Achong, 1979) and nasopharyngeal carcinoma (Klein, 1979). In view of the close relationship between virusneutralizing antibodies and antibody to the EB virus-related membrane antigen (MA) displayed on virus-producing cells (Pearson et aL, 1970(Pearson et aL, , 1971Gergely et al, t971 ;de Schryver et al, 1974), it has been suggested that an MA-based vaccine could provide a means of protecting against EB virus infection (Epstein, 1976).…”

Section: Discussionmentioning

confidence: 99%