HERPESVIRUS

H E R P E S V I R U S

  1. The Herpes Group

    1. HV-1 (Simplex 1): Historically - "above the waist:" "Cold Sores," fever blisters, eye and brain infections
    2. HV-2 (Simplex 2): "Below the waist:" genetal ulceration
    3. HV-3 (Varicella zoster): Chickenpox, shingles, brain infections (Parkinson's Disease)
    4. HV-4 (Epstein-Barr): Infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma
    5. HV-5 (Cytomegalovirus): Mononucleosis, eye, kidney, brain and congenital infections

  2. THE SUPERINFECTING VIRUSES A brief history of experiments that led up to the elucidation of the mechanisms used by this class of viruses.

  3. General Characteristics

    1. Host Ranges: just about everything including some fungi, often with little species specificity.
    2. Sequestration
    3. Gross Anatomy
      1. Capsid
        1. Icosahedral with 162 tubular capsomers; total weight = 1 to 2 x 109 dal
        2. The tegument with short spikes - a product of exiting the host cell membranes
        3. About 49 different proteins have been associated with HV
      2. dsDNA
        1. linear; 0.85 to 1.5 x 108 daltons = approx 105 aa's = 49+ open reading frames.
        2. the group exhibits a wide range of base ratios
        3. short terminal and internal reiterations of terminal sequences with some inversions
        4. multipli-nicked
        5. probably a circular rf-form
        6. two arms that are in random orientation with each other

  4. Infection Cycle

    1. Mechanics
      1. Viropexis (whatever that means!)
      2. Both enveloped and naked nucleocapsids, and their ghosts are produced.
      3. DNA gets into nucleus; sometimes integrates into host chromosomes (a la lambda)
      4. Nucleo-Core is assembled in the nucleus
      5. Envelope (peplos) is often added in the cytoplasm
      6. Reverse viropexis to exit the dying cell

    2. DNA Replication
      1. Host DNA synthesis, if occuring, is slowly shut down.
      2. Host DNA is pushed to nuclear margin.
      3. Most of the synthetases of thymine kinase, etc., are of viral origin
      4. Made in small segments that are later joined together
      5. Incomplete ligation may result in the observed nicks
      6. Highly purified virionic DNA is as infective as impure virionic DNA (means:__)

    3. Transcription (nuclear) and Translation (cytoplasmic)
      1. An effect opposite that of interferon is seen
      2. Both early and late functions are transcribed according to some labs
      3. Clockwork must be encoded in the translation step according to some labs
      4. Proteins migrate back into nucleus for nucleo-core assembly (A:4, above)
      5. Clockwork is encoded in the sequence of the DNA according to other labs

EARLY EXPERIMENTS

  1. The early history overlaps significantly with the discovery of "interferon". Indeed, in a nutshell, herpes viruses usurp the whole interferon anti-viral defense process.

    To start, let us inject some mice with a mild virus - the primary infection. At timed intervals we are going to isolate ribosome subunits from these mice.

    These subunits will be purified via sucrose sedimentation centrifugation:

  2. We have noticed that the mice have been induced to produce a new ribosomal subunit, the 15S particle. Of what function is this, if any? Let's use it in a "Nirenberg System" (in vitro cell-free protein synthesis). The preëxisting 60S and 80S subunits are used PLUS, in the experimental tube (small one to the right), we add the new 15S subunits. Just so that we can easily see if any amino acids are being polymerized into proteins we add radioactive alanine which should soon be found in easily precipitable and macromolecular form.

    As a template, we add various m-RNA's: from normal mouse, or adenovirus transcripts, or synthetic polyU.

    THIS IS THE INTERFERON EFFECT!

  3. Let's move from live mice to live tissue cultures of HeLa cells (cervical cancer cells isolated from "Helen Lane" - not her real name). If we add adenovirus (AV) to the cells, we get lots of virus replication (neatly, AV does not lyse the HeLa cells; it just leaks out).

  4. Now let's try HERPES VIRUS (HV):

    If we look at the supernates:

    Expectedly, we get more AV from the AV-only infected plate, and more HV from the HV-only infected plate. BUT in the doubly infected plate we get mostly HV and only a very little AV! It seems that the HV is capable of suppressing the AV infection.

  5. This warrants another Nirenberg protein synthesis investigation! Only for a bit of variety, we take some cheek epithelial cells from our local elephant and culture them, and then isolate ribosomes from them both before and after inducing them with AV.

    We see that - just like with the mouse system earlier - the elephant reacts just the same.

  6. BUT now let's involve HERPES in this whole process!

    We see that the presence of herpes infection suppresses the reading of all other mRNA's and allows only its own to proceed. Herpes has usurped the interferon effect for its own benefit! WOW!

    I want to go to the TOP OF PAGE or ESCAPE! or go back to the Virology Home Page!