Herpes Virus Flashcards
Intro to Herpesvirus
Known since ancient greece
named from Greek herpein “to creep”
Vital Statistics
Family Herpesviridae
Subfamilies Alpha, Beta, Gamma herpesvirinae
Size 180-200nm
Envelope YES Genome
Linear ds DNA range ~120 kb to ~230 kb
Genome replicated Nucleus
Virus assembly Nucleus
Structure
Glycoproteins:
•Embedded in lipid envelope
•Receptor-mediated entry into cells
Tegument:
•Between envelope and capsid
•Induction of viral gene expression
•Shutoff of host protein synthesis
•Virion assembly
Icosadeltahedral capsid
dsDNA
The Human Herpesviruses
- Herpes simplex virus 1 (HSV-1)
- Herpes simplex virus 2 (HSV-2)
- Human cytomegalovirus (HCMV)
- Varicella-zoster virus (VZV)
- Epstein Barr virus (EBV)
- Human herpesvirus 6A/6B (HHV-6A/6B)
- Human herpesvirus 7 (HHV-7)
- Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8)
Alphaherpesvirinae
HSV-1, HSV-2, VZV
Variable host range
Short replication cycle
Rapid spread in culture
Efficient destruction of infected cells
Betaherpesvirinae
CMV, HHV-6, HHV-7
Restricted host range
Long replication cycle
Slow spread in culture
Gammaherpesvirinae
EBV, KSHV
Restricted host range
Usually specific for B or T lymphocytes
Latent infection in lymphocytes
Replication in culture is infrequent
Herpesvirus cellular tropism
Herpesvirus Target cell
HSV-1 - Mucoepithelial cell
HSV-2 - Mucoepithelial cell
Varicella Zoster virus (VZV) - B lymphocyte, epithelial cell
Cytomegalovirus (CMV) - Epithelial cell, monocytes, lymphocytes
Human herpesvirus 6 (HHV-6) - T lymphocytes
Human herpesvirus 7 (HHV-7) - T lymphocytes
Epstein Barr virus (EBV) - B lymphocyte, epithelial cell
Kaposi’s sarcoma-associated herpesvirus (HHV-8) - B lymphocytes, endothelial cells
Herpesvirus latency and lytic cycle.
Herpesviruses have two parts to their life cycles:
•Latency
•No virus protein expression (modified protein expression)
•Episomal DNA replicated with host cell DNA
•Immunologically silent
•Lytic cycle
•Virus DNA replication
•New progeny viruses made
•Full range of virus proteins expressed
•Highly immunogenic
Herpesvirus binding and entry into host cells
Conserved glycoproteins essential for entry Glycoprotein B (gB) Glycoprotein H (gH) Glycoprotein L (gL) Glycoprotein M (gM) Glycoprotein N (gN)
Fusion with host cells
Not all herpesviruses will go lytic immediately following infection
Herpesvirus lytic replication cascade
Herpesvirus DNA replication
Herpesvirus DNA replication II
Herpesvirus DNA replication III
Herpesvirus DNA replication IV
Herpesvirus DNA replication: Rolling circle
Clinical manifestations of herpes simplex infections
Infection via mucosal surfaces. Replication in oral or genital mucosa. Invasion via sensory nerve endings.
HSV has two unique properties:
•Neurovirulence
•Invade and replicate in the CNS
•Profound disease
•Severe neurologic devastation
•Latency
•HSV-1: Trigeminal ganglion
•HSV-2: Sacral ganglia
Mannifestations in the Immunocompromised
Transplant
•Severity directly related to type of immunosuppressive therapy.
•Pneumonitis, Esophagitis, Gastritis
HIV/AIDS
•More exaggerated
•More frequent
•More resistant to antivirals
Clinical manifestations of Cytomegalovirus infection
HEALTHY:
•Usually clinically silent
•Up to 8% primary infection results in mononucleosis
CONGENITAL CMV:
•In utero infection of multiple systems
IMMUNOCOMPROMISED:
Transplant (solid and hematopoietic stem cell)
•Pneumonitis, Esophagitis, Gastritis, Enterocolitis, Hepatitis, Retinitis, GRAFT-VERSUS-HOST DISEASE
HIV/AIDS
•Retinitis, Esophagitis, Gastritis, Enterocolitis, Peripheral neuropathy, Pneumonitis, Hepatitis
CMV infection and pregnancy
Epstein Barr virus infection
•Up to 95% world population infected by adulthood
•Infection is usually asymptomatic
•Delayed infection can result in infectious mononucleosis (glandular fever)
•B lymphotropic
•EBV maintains latency in memory B cells for the lifetime of the host.
•CD21 (gp350) and HLA class II (gp42)
•Epithelial cells
•Person-to-person transmission of EBV
•T cells and NK cells
•Very rare
Clinical manifestations of Epstein Barr infection
B cell malignancies
•Burkitt lymphoma
•Hodgkin lymphoma
Epithelial cell malignancies
•Nasopharyngeal carcinoma
•Gastric carcinoma (10%)
T and NK cell malignancies
•Extranodal NK/T cell lymphoma
•NK leukaemia
