EBV is most commonly known as the causative agent of IM in young adults. Its initial discovery in association with the childhood disease Burkitt lymphoma (BL) led to its recognition as the first human virus clearly related to a malignancy. More recently, EBV has been associated with several additional human neoplastic diseases.

A. Epidemiology and pathogenesis

Most transmission of EBV occurs by intimate contact with saliva that contains virus during both primary infection and in repeated episodes of asymptomatic shedding. The initial site of virus replication appears to be the oropharyngeal epithelium, following which some of the progeny viruses infect B lymphocytes (Figure 1). The B-cell receptor for EBV is the complement component C3b receptor. During B-cell infection, only a limited number of early proteins are synthesized. Expression of these gene products results in latency and immortalization of the B cell. The EBV genome is maintained as a circular plasmid-like form called an episome during latency. One protein that is expressed during latency is called EBNA1, and one of its key functions is to segregate the episomes into daughter cells following cell division. EBV infection of B cells also causes the induction of a number of cellular lymphokines, including B-cell growth factors. In contrast to other herpesviruses, the early genes of EBV induce cell multiplication and immortalization, rather than cell death. Thus, infection induces a polyclonal B cell proliferation and an accompanying nonspecific increase in total IgM, IgG, and IgA. The IgM class contains heterophile anti bodies that agglutinate sheep and horse red blood cells. These antibodies are the basis for the classic diagnostic test for EBV-associated IM.

Fig1. Pathogenesis of infectious mononucleosis caused by Epstein-Barr virus (EBV).

B. Clinical significance

As stated earlier, primary infection in infancy or childhood is usually asymptomatic, but as many as 50 percent of those infected later in life develop IM. Although B cells are the primary targets of infection as a result of the presence of the EBV-receptor molecule, EBV has more recently been found to be associated with a small number of T-cell malignancies as well. In patients who are immunodeficient or immunosuppressed, the lack of cell-mediated immune control increases the likelihood of lymphoproliferative disorders of various kinds. Throughout life, healthy EBV carriers continue to have episodes of asymptomatic virus shedding. The source of this virus seems to be the productively infected oropharyngeal cells that acquire the virus from latently infected B cells in which the lytic cycle has been activated.

1. Infectious mononucleosis: The manifestations and severity of primary EBV infection vary greatly, but the typical IM syndrome appears after an incubation period of 4 to 7 weeks and includes pharyngitis, lymphadenopathy, fever, splenomegaly, and increased levels of liver enzymes in the blood (Figure 2). Headache and malaise often precede and accompany the dis ease, which may last several weeks. Complete recovery may take much longer.

Fig2. Characteristics of infectious mononucleosis.

 2. EBV and malignancies: Following the initial discovery of EBV in association with BL, it has been shown to be associated with a number of other human neoplastic diseases.

a. Burkitt lymphoma: BL was first described in 1958 as a rather unique malignancy of the jaw, found in an unusually high frequency in children in regions of equatorial Africa. BL cells all contain one of three characteristic chromosome translocations. The breakpoints of these translocations are such that the c-myc proto-oncogene on chromosome 8 is constitutively activated. Malarial infection and HIV infection are known risk factors for development of BL.

 b. Epstein-Barr–associated nasopharyngeal carcinoma: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southeast Asia and North Africa and in the Inuit population, but it is less common elsewhere. NPC differs from BL in that there is no characteristic chromosomal alteration, and the cells involved are epithelial in origin. A role for EBV is suggested because all cells of the tumor contain cytoplasmic viral DNA molecules (episomes).

c. Epstein-Barr virus infections in immunocompromised and immunosuppressed patients: In BL and NPC, EBV infection appears to be only one step in a multistep, disease-causing process, and its specific role is still not well defined. In contrast, EBV alone appears to be sufficient for induction of B-cell lymphomas in immunocompromised patients, such as trans plant recipients and individuals with AIDS, who cannot control the cell multiplication induced by the early proteins. For example, many AIDS patients develop a B-cell malignancy of some type: BL of the sporadic type occurs with high frequency in earlier stages of AIDS progression, whereas non–BL-type lymphoblastic lymphomas are more characteristic in late-stage AIDS patients. Not all of the HIV-associated BL cases contain the EBV genome. AIDS patients infected with EBV may exhibit nonmalignant, white-gray lesions on the tongue (“hairy leukoplakia”) as shown in Figure 3.

Fig3. Hairy leukoplakia caused by Epstein Barr virus infection.

C. Laboratory identification

Atypical lymphocytes (cytotoxic T cells) can be observed in the blood smear of a patient with IM (Figure 4). The classic test for IM, the Paul-Bunnell test, is based upon the nonspecific elevation of all Igs, including heterophile antibodies that specifically agglutinate horse and sheep red blood cells, duringpolyclonal stimulation of B cells by EBV infection. These heterophile antibodies are diagnostic for EBV-related IM, although they are not present in all cases of EBV IM. Antibodies specific for EBV are also produced during infection. IgM and IgG antibodies specific for EBNA1 and capsid proteins can be detected by serological techniques.

Fig4. Abnormal mononuclear cells commonly seen in infectious mononucleosis.

D. Treatment and prevention

 Although acyclovir inhibits EBV replication, none of the antiherpes drugs have been effective in modifying the course or severity of IM due to EBV or in preventing development of EBV-related B-cell malignancies. Acyclovir has been successful in treating oral hairy leukoplakia, in which the virus is actively replicating in the epithelial cells of the tongue. No vaccine for prevention of EBV infections is currently available. Some properties of the common herpesvirus infections are summarized in Figure 5.

Fig5. Properties of common herpesvirus infections.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الصيانة ينفذ أعمال إدامة لإحدى المدارس في محافظة النجف الأشرف

المجمع العلمي يستأنف الختمة القرآنية الأسبوعية في محافظة الديوانية

حملة تطوير وتأهيل تشهدها مدينة الفردوس الترفيهية استعدادًا لاستقبال العوائل

العتبة العباسية المقدسة تطلق فعاليات مهرجان (ترتيل الرأس) السنوي الثاني في بغداد

المزيد

الآخبار الصحية

لون أسنانك يتحدث عن صحتك.. إليك ما يقول

عادة يومية بسيطة تخفض الكوليسترول وتحمي القلب

الزنجبيل.. دواء سحري لحماية القلب

المشروبات شديدة السخونة.. "خطر خفي" يهدد صحتك

المزيد

الآخبار التكنلوجية

كيف يمكن لعادات القيادة السيئة أن تؤثر على قيمة سيارتك

في طوفان الذكاء الاصطناعي.. نصائح لحجز "تذكرة النجاة"

هكذا يسرق "قراصنة الذكاء الاصطناعي" المليارات بطرق بسيطة

فيديو لانفجار كرة نارية في سماء اليابان.. ما تفسير ذلك؟

المزيد

مواضيع ذات صلة

Herpes simplex virus, types 1 and 2

Herpesviridae: Structure and Replication

Adenoviridae

Human Cowpox

Human Monkeypox

Smallpox virus

Papovaviridae: Subfamily Polyomavirinae

Effects of viral infection on the host cell

Assembly and release of progeny viruses

Clinical Syndromes of Adenovirus

JCPyV and progressive multifocal leukoencephalopathy (PML)

Polyomavirus-associated nephropathy (PVAN)