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15.9B: Infectious Mononucleosis - Biology

15.9B: Infectious Mononucleosis - Biology


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Learning Objectives

  • Describe infectious mononucleosis

Infectious mononucleosis is an infectious, widespread viral disease caused by the Epstein–Barr virus (EBV), one type of herpes virus, to which more than 90% of adults have been exposed. Occasionally, the symptoms can recur at a later period. It is sometimes colloquially known as the “kissing disease” from its oral transmission. Most people are exposed to the virus as children, when the disease produces no noticeable or only flu-like symptoms. In developing countries, people are exposed to the virus in early childhood more often than in developed countries. As a result, the disease in its observable form is more common in developed countries. It is most common among adolescents and young adults.

Symptoms

The disease is characterized by fever, sore throat, and fatigue, along with several other possible signs and symptoms, especially in adolescents and young adults. The infection is spread via saliva and has an incubation period of four to seven weeks. Symptoms usually persist for two to three weeks, but fatigue is often more prolonged. Infectious mononucleosis is primarily diagnosed by observation of symptoms, but suspicion can be confirmed by several diagnostic tests. The most commonly used diagnostic criterion is the presence of 50% lymphocytes with at least 10% atypical lymphocytes (large, irregular nuclei), while the person also has fever, pharyngitis, and adenopathy. Infectious mononucleosis is generally self-limiting, so only symptomatic and/or supportive treatments are used. Rest is recommended during the acute phase of the infection.

Once the acute symptoms of an initial infection disappear, they often do not return. But once infected, the patient carries the virus for the rest of his or her life. The virus typically lives dormantly in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the patient is already carrying the virus dormantly.

Key Points

  • Infectious mononucleosis is an infectious disease caused by the Epstein-Barr virus (EBV).
  • Infectious mononucleosis (also called mono or kissing disease) is spread orally and is characterized by symptoms such as fever, sore throat, and fatigue.
  • Once infected, the virus lives dormantly in B lymphocytes in a person.

Key Terms

  • Epstein-Barr virus (EBV): Virus responsible for causing infectious mononucelosis.
  • infectious mononucleosis: An infectious, widespread viral disease caused by the Epstein–Barr virus (EBV), one type of herpes virus. Most people are exposed to the virus as children, when the disease produces no noticeable or only flu-like symptoms.

Abstract

Background: B-cell post transplant lymphoproliferative disorders (PTLDs) encompass a diverse group of entities, the majority representing EBV-driven lymphoproliferations, which arise in the setting of iatrogenic immunosuppression. Their pathogenesis, especially the genetic relationship of PTLD with other types of B-cell non-Hodgkin lymphomas (B-NHLs), is not well understood and the association of polymorphic PTLD (P-PTLD) with monomorphic PTLD (M-PTLD) is presently unclear. Thus, in order to address these issues we analyzed gene expression profiles of PTLD and compared them with those derived from other types of B-NHL, normal B-cell subsets, and B-cell derived cell lines.

Material and methods: Paraffin embedded and H&E stained sections were used for morphologic analysis and PTLD were classified according to the WHO classification. Phenotypic characterization was performed using a comprehensive panel of antibodies and in situ hybridization for EBER. Frozen tissue from PTLD, different B-NHL, purified normal B-cell subsets, EBV-transformed lymphoblastoid cell lines (LCLs) and multiple myeloma cell lines, was used to generate complementary RNA (cRNA) that was hybridized to HGU95 arrays (Affymetrix). Gene expression data were analyzed using unsupervised and supervised clustering algorithms and classifiers were generated to determine the relationship between PTLD and cells corresponding to different stages of mature B-cell development.

Results: The 12 PTLD analyzed represented an infectious mononucleosis-like (IM-like) lesion, 5 P-PTLD, and 6 M-PTLD. All P-PTLD and 5 M-PTLD had late-germinal center (GC)/post-GC phenotypes and 8 PTLD, including the IM-like lesion, were EBV+, while 4 PTLD were EBV−. The expression profiles of late GC/post GC PTLD appeared homogeneous and distinct from other B-NHL, however no segregation of P-PTLD and M-PTLD or EBV+ and EBV− PTLD was noted. Surprisingly, on supervised analysis, only 4 genes were expressed at higher levels in PTLD compared to B-NHL and normal B-cell subsets (BLIMP-1, XBP-1, IFITM3, PCMT1) and only 2 genes were differentially upregulated in EBV+ PTLD (CD27 ligand, MTDH). The expression profiles of PTLD appeared most similar to LCLs.

Conclusions: B-cell PTLDs of late-GC/post-GC phenotype represent a distinct type of B-NHL, which are possibly derived from activated B-cells. Despite morphologic distinctions, P-PTLD and M-PTLD have overlapping genetic profiles suggesting disease heterogeneity within different categories.

Disclosure: No relevant conflicts of interest to declare.


15.9B: Infectious Mononucleosis - Biology

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      Affiliations

      Department of Nutrition, Harvard School of Public Health, 677 Huntington Avenue, Boston, 02115, MA, USA

      Alberto Ascherio & Kassandra L. Munger

      Department of Neuroinflammation, Institute of Experimental Immunology, University of Zürich, Winterthurer Strasse 190, Zurich, 8057, Switzerland

      You can also search for this author in PubMed Google Scholar

      You can also search for this author in PubMed Google Scholar

      You can also search for this author in PubMed Google Scholar

      Contributions

      The authors contributed equally to researching data for the article, providing substantial contribution to discussion of the content, writing the article, and to review and/or editing of the manuscript before submission.


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