Latent Viruses Flashcards
1
Q
Persistent/Latent Viruses
A
- Remain for the life of their immunocompetent hosts
- Often w/o causing any sx
- Virus–host balance can be disrupted by imbalances in immune response, genetic or environmental factors
- Major source of morbidity and mortality
- Cause a variety of pathologies including virus-associated cancers
- Cause life-threatening viral replicative infections in immunocompromised
2
Q
Epstein-Barr Virus (EBV)
Overview
A
- EBV is a human herpes virus (HHV)
- EBV infection has 3 potential outcomes:
- Replicate in B-cells or epithelial cells
- Latent infection of memory B-cells in the presence of competent T-cells
- Stimulate growth and immortalize B-cells
3
Q
Epstein-Barr Virus (EBV)
Classification and Morphology
A
- Human herpes viruses (HHV-4)
- Enveloped, icosadeltahedral nucleocapsid symmetry w/ linear dsDNA
- Classified into 3 subfamilies based on genomic structure, tissue tropism, cytopathology, site of infection, and pathogenesis/symptomology
-
Gamma herpes viruses
- Very restricted host range
- Intermediate replication time
- Latently infect cells of the lymphoid system
- EBV is the only human virus in this group
4
Q
Epstein-Barr Virus (EBV)
Lifecycle
A
- Replicates in permissive cells in the oropharynx ⇒ lytic EBV replication
- Infectious virus is detected in the saliva
- Human disease generally ass. w/ 1° infection of EBV is mononucleosis
- After OP infection, naive resting B-cells in the tonsils are infected
- Latent infection in long-lived memory B-cells
- Host cells and type of infection linked:
- Mucosal epithelial cells ⇒ lytic infection
- B-cells ⇒ latent infection
5
Q
Epstein-Barr Virus (EBV)
Immune Response
A
- T-cells stimulated by infected B-cells ⇒ kill and limit B-cell outgrowth
- T-cells required for controlling infection
- Host T-cell surveillance important for preventing EBV pathogenesis
- ↑ Incidence of potentially fatal lymphoproliferative lesions in pts receiving immunosuppressive therapy s/p organ transplants
- Can be reversed by infusion of EBV-specific immune T-cells
- Ab role is limited
6
Q
Epstein-Barr Virus (EBV)
Epidemiology and Transmission
A
- EBV carried by > 90% of adult human population worldwide
- EBV infection transmitted in saliva ⇒ “kissing disease”
- EBV-specific immunity is lifelong
- Co-factors for EBV-associated neoplasms are suggested by epidemiological findings
7
Q
Epstein-Barr Virus (EBV)
Pathogenesis
A
- EBV infection of B-cells ⇒ viral shedding ⇒ host-to-host transmission and viremia
- Viral gene expression ⇒ ⊕ B-cell growth, ⊗ apoptosis ⇒ B-cell immortalization
- T-cells limit B-cell outgrowth
- Absence of T-cell regulation ⇒ lymphoproliferative disease
- Diseases of EBV result from either:
- An overactive immune response ⇒ infectious mononucleosis
- Lack of effective immune control ⇒ lymphoproliferative diseases and cancers
8
Q
Epstein-Barr Virus (EBV)
Clinical Presentation
A
-
Infectious mononucleosis is rarely fatal
- Milder in children vs adults
-
EBV-associated lymphoproliferative diseases
- Generally d/t B-cell proliferation w/o T-cell control
-
EBV ass. w/ several tumors of B-cell origin & other cell types including:
- Post-transplant lymphoproliferative disease
- Burkitt’s lymphoma
- Hodgkin’s lymphoma
- T/NK cell lymphomas
- Nasopharyngeal carcinoma, Hairy cell oral leukoplakia
- Gastric carcinoma
9
Q
Infectious Mononucleosis
Overview
A
- B-cell overgrowth controlled by a normal T-cell response to B-cell proliferation and EBV antigenic peptides
- B-cells present EBV Ag on both MHC I and MHC II
- Activated T-cells appear as atypical lymphocytes ⇒ Downey cells
- ↑ # in peripheral blood during 2nd week of infection
- 10-80% of total WBCs at this time
- ↑ # in peripheral blood during 2nd week of infection
10
Q
Infectious Mononucleosis
Clinical Manifestations
A
Sx results mainly from activation and proliferation of T-cells:
Classic triad: lymphadenopathy, splenomegaly, and exudative pharyngitis
- Classic lymphocytosis ⇒ ↑ mononuclear cells
- Swelling of lymphoid organs (lymph nodes, spleen, and liver)
- Malaise and fatigue ⇒ a large amount of energy is required to power the T-cell response
- Sore throat ⇒ response to EBV-infected epithelium and B-cells in the tonsils and throat
- ± Rash, esp. after ampicillin tx (for a possible strep throat)
- Children w/ less active immune response to EBV infection ⇒ mild disease
11
Q
Epstein-Barr Virus (EBV)
Lymphoproliferative Diseases
A
- EBV infection in pts w/o T-cell immunity ⇒ polyclonal leukemia-like B-cell proliferative disease and lymphoma, instead of mononucleosis
- Transplant pts on immunosuppressive tx @ high risk for post-transplant lymphoproliferative disease
- New exposure to EBV or reactivation of latent virus
- Disease dissipates on reduction of immunosuppression
12
Q
Epstein-Barr Virus (EBV)
Chronic Diseases
A
-
African Burkitt Lymphoma
- Poorly differentiated monoclonal B-cell lymphoma of the jaw and face
- Endemic in children living in the malarial regions of Africa
-
Burkitt Lymphoma
- Tumor cells derived from lymphocytes
- Hodgkin’s Lymphoma
-
Nasopharyngeal Carcinoma
- Endemic in adults in Asia
- Tumor cells are epithelial in origin
-
Hairy Cell Oral Leukoplakia
- Unusual manifestation of a productive EBV infection of epithelial cells
- Characterized by lesions of the tongue and mouth
- Opportunistic manifestation in pts w/ AIDS
13
Q
Epstein-Barr Virus (EBV)
Diagnosis
A
- Based on sx, blood work, heterophile Ab, and EBV-specific Ab
- Sx include HA, fatigue, fever, and classic triad of lymphadenopathy, splenomegaly, and exudative pharyngitis
-
CBC
- Leukocytosis
-
Downey cells (atypical lymphocytes)
- Appear w/ onset of sx
- Disappear w/ resolution of disease
-
Heterophile Ab ⇒ IgM
- Made by nonspecifically-activated, proliferating B-cells
- Reacts w/ Paul-Bunnell Ag on sheep, horse, and bovine RBCs
- Can usually be detected by end of 1st week of illness
- Lasts for as long as several months
- Basis for Monospot agglutination test
- Often not present in children w/ infectious mononucleosis
-
EBV-specific Ab
- Appear at different times post-infection
- Used to distinguish b/t 1° infection and reactivation
- ⊖ VCA Ab ⇒ no infection & person is susceptible
-
⊕ Anti-VCA IgM ⇒ early EBV infection
- Appears early in EBV infection and usually disappears w/in 4-6 weeks
- ⊕ IgG vs viral capsid antigen (VCA) and Epstein Barr Nuclear Antigen (EBNA) ⇒ previous infection
-
Anti-VCA IgG
- Appears in the acute phase of EBV infection
- Peaks at 2-4 weeks after onset
- Declines slightly then persists for the rest of a person’s life
-
Ab to EBNA
- Not seen in the acute phase of EBV infection
- Slowly appears 2-4 months after onset of sx
- Persists for the rest of a person’s life
14
Q
Epstein-Barr Virus (EBV)
Treatment/Prevention
A
- No specific tx available for EBV infection
- Vaccines specific to gp350 and EBV-specific CTL epitopes under development
- Ubiquitous nature & potential for asymptomatic shedding makes control difficult
- Infection elicits lifelong immunity
- Exposure to virus early in life better b/c disease is more benign in children
15
Q
Human T-Cell Lymphotropic Virus Type 1 (HTLV-1)
Overview
A
- Leukemia virus characterized by a long latency period (> 30 years)
-
Associated with:
- Tropical spastic paraparesis (TSP) ⇒ degenerative neurologic disorder
- Adult T-cell leukemia/lymphoma (ATLL)
- HTLV-1-associated myelopathy (HAM)
20
Q
Adult T-cell Leukemia/Lymphoma (ATLL)
Overview
A
Malignant lymphoma/leukemia of CD4+ T-cells
- Progression to ATLL can take 30-50 years
- Can be acute or chronic
- Incidence of ATLL is greater in males
- Characterized by leukemic T-cells, skin lesions, and abnormal lymph nodes
- Usually monoclonal but can be polyclonal
- Malignant cells called “flower cells” ⇒ pleomorphic w/ lobulated nuclei
- Usually fatal w/in 1 year of dx, regardless of tx
