DNA VIRUSES DNA Enveloped Viruses I Objectives In

DNA VIRUSES DNA Enveloped Viruses I

Objectives • In this lecture you will learn about properties, pathogenesis, clinical picture and diagnosis of: • Herpesviruses (HHVs 1 to 8) • Poxviruses – Smallpox Virus – Vaccinia virus – Molluscum contagiosum virus

Herpesviruses Properties: • All Herpesviruses are structurally similar: • Enveloped (the envelope contains viral glycoprotein spikes and Fc receptors) • Icosahedral symmetry • The genome is linear double stranded DNA (there is about 50% homology between the genome of HSV 1 and HSV 2, and between that of HSV 6 and HSV 7).

Herpesviruses Properties: • The virion does not contain a polymerase • Large in size (150 -200 nm in diameter) • They replicate in the nucleus forming intranuclear inclusions. • They are the only viruses that obtain their envelope by budding from the nuclear membrane • They establish latent infections and persist indefinitely in infected hosts.

Herpesviruses Classification Depending on the biological property of the genus herpes viruses were subdivided into three subfamilies: 1. Alphaherpesviruses: fast-growing, cytolytic viruses and latency in the neurons. Includes HHV-1, HHV-2 (HSV-1 and 2 respectively) and HHV-3 (VZV)

Herpesviruses Classification 2. Betaherpesviruses: Slow-growing, cytomegalic, and latency in the glands and kidneys includes CMV (HHV-5), but roseoloviruses (HHV-6 and HHV-7 are lymphoproliferative and latency in the lymphoid tissue)

Herpesviruses Classification 3. Gammaherpesviruses: Variable in their growth rate, have lymphoproliferative effect on cell , and latency in the lymphoid tissue, includes EBV (HHV-4) and Kaposi’s sarcoma-associated herpesvirus (HHV-8)

1 -Herpes simplex viruses (HSV) HSV types 1 and 2 are distinguished by two main criteria: • Antigenicity and Location of infection; lesions caused by HSV-1 are generally above the waist while those caused by type 2 are below the waist

1 -Herpes simplex viruses (HSV) Diseases HSV-1 causes: 1) Gingivostomatitis, (also in the primary infection may cause tonsillitis and pharyngitis) 2) Recurrent herpes labialis (cold sore) usually mild lesion. 3) Keratoconjunctivitis: if the primary infection in the eye there will be severe kerato-conjunctivitis, and recurrent lesion is common and may cause corneal ulcer.

1 -Herpes simplex viruses (HSV) Diseases HSV-1 causes: 4) Encephalitis (Fatal) HSV-1 is considered to be the most common cause of sporadic encephalitis. 5)Disseminated infection in immunocompromised patients (mainly involve the respiratory tract, esophagus and GIT.

HSV-1

1 -Herpes simplex viruses (HSV) Diseases: HSV-2 causes: 1)Genital herpes 2)Neonatal herpes 3)Aseptic meningitis.

1 -Herpes simplex viruses (HSV) Modes of transmission: HSV-1 is transmitted primarily in saliva whereas HSV-2 is transmitted by sexual contact. As a result HSV-1 infections occur mainly on the face whereas HSV-2 infections occur in the genital area.

1 -Herpes simplex viruses (HSV) Pathogenesis: The virus replicates at the initial site of infection; skin or mucous membrane, then migrates up the neuron and become latent in the sensory ganglia. HSV-1 becomes latent in the trigeminal ganglia; HSV-2 becomes latent in the lumber and sacral ganglia.

1 -Herpes simplex viruses (HSV) Pathogenesis: The virus is activated from the latent state by a variety of inducers, e. g, sun light, hormonal changes, trauma, stress and fever, at which time it migrates down the neurons and replicates in the skin causing lesions. The typical lesion is vesicle. Multinucleated giant cells are typically found at the base of herpes lesions.

1 -Herpes simplex viruses (HSV) Diagnosis: • 1) Clinically the herpes lesion is characteristic. • 2) Most important diagnostically is isolation of the virus from the lesion by growth in cell culture. • 3) A rapid diagnosis by Tzanck smear by staining the cells from the base of the vesicle with Giemsa stain, the presence of multinucleated giant cells suggests herpes infection. • 4) A rapid diagnosis of encephalitis can be made by detecting HSV-1 DNA in the spinal fluid using PCR assay.

1 -Herpes simplex viruses (HSV) Treatment: • 1. Systemic acyclovir can be used in treating HSV-1 encephalitis and systemic disease in immunocompromised patients. Also it can be used locally to treat primary and recurrent genital herpes. • 2. Foscarnet can be used in cases resistant to acyclovir.

1 -Herpes simplex viruses (HSV) Prevention • Involves recommending Cesarean section in women who have sever genital lesions. • Vaccination is still experimental (using purified envelope glycoprotein antigens).

2 -Varicella-Zoster virus (VZV) Diseases • Varicella (Chickenpox): is the primary disease, after incubation period of 14 -21 days, brief prodromal symptoms of fever, malaise. A papulovesicular rash then appear in crops on the trunk then spread to the head and extremities. Itchy and ends by crusting.

2 -Varicella-Zoster virus (VZV) Diseases • Zoster (Shingles): usually occur in immunocompromised persons as a result of disease or therapy or aging. It is the recurrent form, occurs as painful vesicles along the course of the sensory nerve in the head or trunk.

2 -Varicella-Zoster virus (VZV) Pathology and pathogenesis Varicella: the route of infection is the mucosa of upper respiratory tract or conjunctiva: • 1. The initial replication in regional LN • 2. Primary viremia • 3. Virus replicate in the liver and spleen • 4. Then secondary viremia involving infected mononuclear cells • 5. The virus transported to the skin where the typical rash develop.

2 -Varicella-Zoster virus (VZV) Pathology and pathogenesis • Zoster: waning of the immunity usually is the trigger for the latent virus to replicate in the ganglia and migrate through the sensory nerves to the skin causing intense inflammation and pain

2 -Varicella-Zoster virus (VZV) Diagnosis • 1) Most diagnosis is made clinically. • 2) Tzanck smear • 3) definitive diagnosis is isolation of the virus from the lesion by growth in cell culture. • 4)Virus specific Ab can be detected using fluorescent Ab and enzyme immunoassay.

2 -Varicella-Zoster virus (VZV) Treatment: • No antiviral therapy is necessary for chickenpox or shingles in immunocompitant children, acyclovir of famciclovir can be used if these lesions occur in immunocompitant adults with moderate or severe infections. Prevention: • Live attenuated VZV vaccine is effective in children (80 -85% protection) but only 70% protection rate in adults.

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