HERPESVIRIDAE

on 2.2.09 with 1 comment



  • STRUCTURE: ds-DNA, linear, enveloped.

    • Tegument: Amorphous protein structure that surrounds the capsid.

  • DIAGNOSIS: Cell culture will show intranuclear inclusion bodies.

  • ALPHA-HERPES VIRUSES: Grow very rapidly, have a broad host-range. Latency is usually in neural tissue.

    • REPLICATION: Occurs in the nucleus.

      • HSV-1 and HSV-2 binds to a heparin sulfate receptor, present on every cell in the body.

      • Immediate Early Genes:

        • alpha-Trans inducing Protein, associated with the tegument, induces the production of the immediate early genes.

        • The protein-products from these genes are transported back into the nucleus, where they induce transcription of the delayed early genes.

      • Delayed Early Genes: Encodes about 15 proteins involved in viral DNA replication, including DNA polymerase and Thymidine kinase. Viral DNA replication then occurs.

      • Late Genes: They encode structural proteins, formed after DNA replication is complete. More than 50% of formed virions are released from cell.

    • HERPES SIMPLEX:

      • STRUCTURE: More than 8 glycoproteins on viral envelope. HSV-1 and HSV- show about 50% antigenic relatedness.

      • PATHOGENESIS:

        • Acute infection is usually local, producing vesicles which are infectious and often ulcerate.

        • Latent Infection: Virus travels up neuron to ganglion where it becomes latent.

          • During latent infection, the virus does not replicate. Only a set of genes called latency-associated transcripts (LAT) are transcribed.

          • For oral Herpes (HSV-1), the virus remains latent in the Trigeminal Ganglion.

          • Reactivation can occur as a result of stress, immunosuppression, illness, etc.

      • DIAGNOSIS: Look for Cytopathic Effect (CPE) 24-36 hrs after inoculation of vesicular sample in tissue culture.

        • Can see multinucleated Giant cells.

        • Can use Neutralization Test or immunofluorescence.

      • HERPES SIMPLEX 1 (HHV-1, HSV-1): Infection usually occurs early in childhood, and in some communities more than 90% seroconversion is seen by age 10.

        • MANIFESTATIONS:

          • Encephalitis: Acute febrile disease.

          • Keratoconjunctivitis: May result in permanent corneal damage and visual impairment.

          • Acute Herpetic Gingivostomatitis: Almost always caused by HSV-1. Happens in toddlers.

          • Herpes Labialis: Primarily HSV-1, but both can infect.

      • HERPES SIMPLEX 2 (HHV-2, HSV-2):

        • Due to cross-reactivity, individuals with HSV-1 infection get a milder form of HSV-2 infection.

        • MANIFESTATIONS:

          • Genital Herpes: Primarily HSV-2, but both can infect.

            • May be associated with fever, malaise, and inguinal lymphadenopathy.

            • Virus goes up and remains latent in lumbo-sacral ganglia.

          • Neonatal Herpes: Perinatal transmission of HSV-2, during an active infection, through the birth canal. Outcome can range from subclinical to severe.

          • Proctitis:

          • Meningitis:

          • Whitlow: HSV-1 or HSV-2. Infection of fingers in healthcare personnel or kiddies who suck their thumbs.

      • TREATMENT:

        • Idoxuridine: Topical ointment

        • Ara-A: Older drug inhibits DNA replication, but it's toxic. Used for encephalitis, or topically for keratitis.

        • IUDR: Acts on DNA replication and is too toxic to use systemically.

        • Acyclovir: Converted into triphosphate form by viral Thymidine Kinase. It blocks viral DNA polymerase and is virtually non-toxic. It does not cure latent infection but it's great for symptomatic infections.

    • VARICELLA-ZOSTER VIRUS (HHV-3, VZV):

      • REPLICATION: Daughter virions remain largely cell-associated.

      • TRANSMISSION is probably respiratory. Nasal mucosa.

      • PATHOGENESIS:

        • Latent Infection: VZV virus remains latent in dorsal root ganglion, where it can later reactivate to form Zoster.

      • MANIFESTATIONS:

        • Chicken-Pox (Varicella):

          • Symptoms: Fever and malaise. Rash starts on trunk and spreads outward to extremities.

          • In early infection, eosinophilic inclusion bodies are found in nuclei of infected cells.

          • Complications:

            • Encephalitis is a rare complication, associated with increased mortality (10%) and permanent CNS residual damage (10%).

            • Varicella Pneumonia: Rare in children; 20-30% of adults.

        • Shingles (Zoster): Reactivation infection, occurs (usually) unilaterally over a single dermatome, often over the face.

          • Skin lesions identical to Varicella.

  • BETA-HERPES VIRUSES: Grow slowly, have a narrow host range, latency in various tissues.

    • CYTOMEGALOVIRUS (HHV-5, CMV):

      • REPLICATION: About 25% of infected virions leave the cell.

      • PATHOGENESIS:

        • Primary infection is usually asymptomatic.

        • Found in cervix of up to 10% of healthy women.

      • EPIDEMIOLOGY:

        • 50-70% of women of child-bearing age are seropositive.

        • Pregnant women usually have subclinical infection. 10-15%

        • CMV is the most common agent of congenital infection, about 1% of all live births.

      • MANIFESTATIONS:

        • In children, may see hepatitis, interstitial pneumonitis, or acquired hemolytic anemia.

        • Cytomegalic Inclusion Disease: Congenital CMV infection. Either intrauterine or early post-natal infection with CMV.

          • May be asymptomatic, or result in mental retardation or death.

          • Large intranuclear inclusions can be seen on histo, in salivary glands, liver, pancreas, kidneys, endocrine glands, brain.

        • Infectious Mononucleosis: CMV is responsible for 10% of cases. It differs from EBV Mono in that you won't see heterophil antibodies.

        • IMMUNOCOMPROMISED:

          • CMV Pneumonitis or hepatitis is common, or occasionally generalized disease.

          • CMV infection is frequently seen in transplant patients.

      • TREATMENT: Ganciclovir

        • Acyclic analog of guanosine inhibits CMV DNA Polymerase.

          • In Immunocompromised, the drug is good for CMV retinitis, esophagitis, and colitis, and less effective for CMV pneumonitis.

      • VACCINE: Live vaccine under clinical trials.

    • HUMAN HERPES VIRUS 6 (HHV-6): Infects T-Cells and monocytes, producing a latent infection.

      • MANIFESTATIONS:

        • Roseola (Exanthem Subitum): HHV-6 has etiological role in this childhood disease. Child presents with drastically high fever for 3-4 days, followed by rash all over body.

        • Fever, encephalitis, hepatosplenomegaly are all possible.

        • Persistent lymphadenopathy, fatigue and malaise may happen in adults.

        • Fatal Fulminant Hepatitis: HHV-6 was isolated from one infant with this disease.

    • HUMAN HERPES VIRUS 7 (HHV-7): Not much known. T-Cells are primary target, and it may cause some cases of childhood roseola.

  • GAMMA-HERPES VIRUSES: Intermediate growth speed, lymphotropic viruses that infect B and T cells.

    • EPSTEIN-BARR VIRUS (HHV-4, EBV):

      • REPLICATION:

        • EBV binds complement receptor CR2 on B-Cells to gain access to cell.

        • About 25% of infected virions leave the cell.

      • PATHOGENESIS:

        • EBV infects and immortalizes human B-Cells. This can result in B-Cell transformation, as in Burkitt's Lymphoma.

        • Infected cells contain multiple virions and express viral antigens. Expressions of these antigens may occur alone, or in conjunction with a productive infection of viral particles.

          • Lymphocyte-detected Membrane Antigen (LYDMA)

          • EBV-Specific Nuclear Antigen (ESNA)

      • DIAGNOSIS: Monospot Test. Look for antibodies against sheep RBC's. If you see hemagglutination, then the antibodies are present and the test is positive.

      • MANIFESTATIONS: Generally ubiquitous virus usually infects in early childhood.

        • Infectious Mononucleosis: Results when initial infection occurs at a later time. EBV causes polyclonal activation of B-Cells.

          • Heterophil Antibodies: Infected B-Cells make these antibodies, which are directed against whatever antigen to which the B-Cell has been sensitized.

          • Atypical Lymphocytes: Activated T-Cells. In response to the B-Cells, the T-Cells proliferate, leading to fever and lymphadenopathy. The T-Cells get activated and form atypical lymphocytes.

          • In the end, the B-Cell is put under control and infection stops. Virus becomes latent in B-Cells.

        • IMMUNOCOMPROMISED: Particularly susceptible to reactivation disease. May see invasive lymphomas, or EBV lesions of mouth called hairy leukoplakia.

        • Burkitt's Lymphoma: Malignant tumor of jaw and face, usually found in kids in Africa.

          • Results from translocation of c-Myc oncogene next to an IgG gene in B-Cells, as a result of EBV infection.

        • Nasopharyngeal Carcinoma: In adults, endemic to China.

      • VACCINE: Vaccine against C3B complement receptor is under development.

    • HUMAN HERPES VIRUS 8 (HHV-8):

      • MANIFESTATIONS: Kaposi Sarcoma.

      • TRANSMISSION: HHV-8 is probably sexually transmitted.

Category: Microbiology Notes

POST COMMENT

1 comments:

Shady Grove Eye Vision Care said...
July 14, 2009 at 7:08 AM

Anti-viral drugs commonly used to treat CMV retinitis are ganciclovir (Cytovene), foscarnet (Foscavir) and cidofovir (Vistide). These medications can slow down the progression of CMV, but they can't cure it. These potent anti-viral drugs can also cause unpleasant or serious side effects.

Post a Comment