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Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state.
J Virol 1994; 68(11):7374-85JV

Abstract

Epstein-Barr virus (EBV) can display different forms of latent infection in B-cell lines in vitro; however, the types of infection normally established by the virus in vivo remain largely unexplored. Here we have approached this question by analyzing the types of viral RNAs present in mononuclear cells freshly isolated from the blood of 14 infectious mononucleosis patients undergoing primary EBV infection and 6 long-term virus carriers. Reverse transcription-PCR amplifications were carried out with a panel of oligonucleotide primers and probes which specifically detect (i) the EBER1 RNA common to all forms of latency, (ii) transcripts either from the Cp and Wp promoters generating all six nuclear antigen (EBNA1, -2, -3A, -3B, -3C, -LP) mRNAs or from the Fp promoter generating a uniquely spliced EBNA1 mRNA, (iii) the latent membrane protein (LMP1 and 2A) mRNAs, and (iv) the BZLF1 mRNA, an immediate-early marker of lytic cycle. Viral transcription in infectious mononucleosis mononuclear cells (and in the B-cell-enriched fraction) regularly included the full spectrum of latent RNAs seen during EBV-induced B-cell growth transformation in vitro, i.e., EBER1, Cp/Wp-initiated EBNA mRNAs, and LMP1/LMP2 mRNAs, in the absence of lytic BZLF1 transcripts. In addition, transcripts with the splice pattern of Fp-initiated EBNA1 mRNA, hitherto seen only in vivo in certain EBV-positive tumors, were frequently detected. In long-term virus carriers, the mononuclear cells were again positive for latent (EBER1) and negative for lytic (BZLF1) markers; Cp/Wp-initiated RNAs were not detected in these samples, but in several individuals it was possible to amplify both Fp-initiated EBNA1 mRNA and LMP2A mRNA signals. We suggest (i) that primary infection is associated with a transient virus-driven expansion of the infected B-cell pool through a program of virus gene expression like that seen in in vitro-transformed cells and (ii) that long-term virus carriage is associated with a switch from Cp/Wp to Fp usage and thus to a more restricted form of latent protein expression that may render the infected cells less susceptible to recognition by the virus-specific cytotoxic T-cell response.

Authors+Show Affiliations

Department of Cancer Studies, University of Birmingham, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7933121

Citation

Tierney, R J., et al. "Epstein-Barr Virus Latency in Blood Mononuclear Cells: Analysis of Viral Gene Transcription During Primary Infection and in the Carrier State." Journal of Virology, vol. 68, no. 11, 1994, pp. 7374-85.
Tierney RJ, Steven N, Young LS, et al. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J Virol. 1994;68(11):7374-85.
Tierney, R. J., Steven, N., Young, L. S., & Rickinson, A. B. (1994). Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. Journal of Virology, 68(11), pp. 7374-85.
Tierney RJ, et al. Epstein-Barr Virus Latency in Blood Mononuclear Cells: Analysis of Viral Gene Transcription During Primary Infection and in the Carrier State. J Virol. 1994;68(11):7374-85. PubMed PMID: 7933121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. AU - Tierney,R J, AU - Steven,N, AU - Young,L S, AU - Rickinson,A B, PY - 1994/11/1/pubmed PY - 1994/11/1/medline PY - 1994/11/1/entrez SP - 7374 EP - 85 JF - Journal of virology JO - J. Virol. VL - 68 IS - 11 N2 - Epstein-Barr virus (EBV) can display different forms of latent infection in B-cell lines in vitro; however, the types of infection normally established by the virus in vivo remain largely unexplored. Here we have approached this question by analyzing the types of viral RNAs present in mononuclear cells freshly isolated from the blood of 14 infectious mononucleosis patients undergoing primary EBV infection and 6 long-term virus carriers. Reverse transcription-PCR amplifications were carried out with a panel of oligonucleotide primers and probes which specifically detect (i) the EBER1 RNA common to all forms of latency, (ii) transcripts either from the Cp and Wp promoters generating all six nuclear antigen (EBNA1, -2, -3A, -3B, -3C, -LP) mRNAs or from the Fp promoter generating a uniquely spliced EBNA1 mRNA, (iii) the latent membrane protein (LMP1 and 2A) mRNAs, and (iv) the BZLF1 mRNA, an immediate-early marker of lytic cycle. Viral transcription in infectious mononucleosis mononuclear cells (and in the B-cell-enriched fraction) regularly included the full spectrum of latent RNAs seen during EBV-induced B-cell growth transformation in vitro, i.e., EBER1, Cp/Wp-initiated EBNA mRNAs, and LMP1/LMP2 mRNAs, in the absence of lytic BZLF1 transcripts. In addition, transcripts with the splice pattern of Fp-initiated EBNA1 mRNA, hitherto seen only in vivo in certain EBV-positive tumors, were frequently detected. In long-term virus carriers, the mononuclear cells were again positive for latent (EBER1) and negative for lytic (BZLF1) markers; Cp/Wp-initiated RNAs were not detected in these samples, but in several individuals it was possible to amplify both Fp-initiated EBNA1 mRNA and LMP2A mRNA signals. We suggest (i) that primary infection is associated with a transient virus-driven expansion of the infected B-cell pool through a program of virus gene expression like that seen in in vitro-transformed cells and (ii) that long-term virus carriage is associated with a switch from Cp/Wp to Fp usage and thus to a more restricted form of latent protein expression that may render the infected cells less susceptible to recognition by the virus-specific cytotoxic T-cell response. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/7933121/Epstein_Barr_virus_latency_in_blood_mononuclear_cells:_analysis_of_viral_gene_transcription_during_primary_infection_and_in_the_carrier_state_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=7933121 DB - PRIME DP - Unbound Medicine ER -