Morbillivirus: Measles

							S. A Moyer                                                                     (-) RNA viruses II


                                     Paramyxoviruses

Morbillivirus:                                               Measles
Paramyxovirus:                                      Parainfluenza Viruses 1 to 4, Mumps
Pneumovirus:                                           Respiratory syncytial virus

I. General Characteristics
   A. Physical properties - enveloped virus.
      1. Single stranded, negative (-) strand RNA, encodes 6 proteins.
      2. RNA-dependent RNA polymerase - P and L protein subunits.
      3. Nucleocapsid protein (N) - helical nucleocapsid.
      4. Membrane (M) protein.
      5. Glycoproteins.
         a. Hemagglutinin (Neuraminidase) (HN), in measles only H- required for attachment.
         b. Fusion protein (F).
   B. Virus reproduction - entirely cytoplasmic.
      1. Attachment by HN protein to cells - neutralizing antibody is directed against H(N).
      2. Fusion of viral envelope with cell membrane via F protein giving giant cell formation
         (syncytia); need antibody to F to prevent spread of virus from cell to cell.
      3. Transcription of individual mRNAs by viral encoded RNA polymerase within virions
         responsible for initial viral protein synthesis.
      4. RNA replication - more protein synthesis - viral assembly.
      5. Budding of virus from plasma membrane of infected cell.

II. Measles infection
    A. Measles is one of the classical childhood exanthems (eruptive diseases) which include
        rubella togavirus), roseola (HHV 6), fifth disease (parvovirus, B19, erythema
     infectiosum) and chickenpox (herpes zoster).
    B. Host range limited to humans, one serotype, and contagion period precedes symptoms.
         Infections are disseminated and characterized by extensive viremia
    C. Transmission - extremely contagious, rarely an inapparent infection, spread by
    respiratory secretions, more severe in adults than children.
    D. Respiratory phase - sore throat, cough, malaise, 5-9 days. Koplik spots - red with white
    centers on inside of mouth.
    E. Systemic phase symptoms.
         1. Replicate in lymph nodes, then into blood - viremia.
         2. Rash - 14 days, spreads from forehead down trunk and out extremities, due to
        replication of virus in skin and mostly to immune response to infection.
         3. Pneumonia associated with measles, both viral and bacterial; atypical measles
        pneumonia - due to an early inactivated viral vaccine (1963-67).
    F. CNS complications.
        1. Acute post-infectious encephalitis (or ADEM- acute disseminated encephalomyelitis)-
        5-7 days after rash, immune response.
        2. Measles inclusion body encephalitis (MIBE).
        3. SSPE - subacute sclerosing panencephalitis, years after infection , mutant virus, lethal
            persistent brain infection.
    G. Vaccine.
        1. One serotype, live virus vaccine injected, MMR - measles (Edmonston strain),
        mumps, rubella, mass vaccination starting in 1970.
        2. Some side effects-fever, rash (5-10%).
        3. Antibody response good, but not lifelong as in natural infection. Revaccinate at 18-20
            yrs.
    H. The CDC WEB page for measles: http://www.cdc.gov/nip/diseases/measles/default.htm
    I. The MMR vaccine WEB page - all issues (great reference for both measles and mumps)
        3. http://www.cdc.gov/nip/vaccine/MMR/default.htm
        4. The vaccination policy current recommendations:
            http://www.cdc.gov/mmwr/preview/mmwrhtml/00000805.htm
Summary: Revised latest updated recommendations of the Advisory Committee on
Immunization Practices (ACIP) on measles, mumps, and rubella prevention. The
recommendations include a basic change in the routine childhood vaccination schedule from a
one-dose to a two-dose schedule using combined measles-mumps-rubella (MMR) vaccine.
Routine revaccination will generally be implemented one age group at a time starting with school
enterers. New recommendations are also included for vaccination of preschool children at high
risk of contracting measles, for students in colleges and other institutions of higher education, for
health-care personnel and international travelers, and for outbreak control.

III. Mumps infection
     A. Host range limited to humans, one serotype and contagion period precedes symptoms.
        Causes acute, but benign swelling of parotid gland, tests and CNS). Infections are
        disseminated and characterized by acute viremia.
     B. Transmission by respiratory secretions - less contagious, 30% inapparent infections.
     C. Respiratory phase - sore throat, cough.
     D. Systemic phase symptoms.
        1. Virus replicates in lymph nodes, then into blood - viremia.
        2. Primary target organ is infection and swelling parotid (salivary) gland at 18-21
           days, 10% not bilateral, some have no swelling at all. Swelling due to edema and
           local inflammatory response.
        3. Testes, ovaries. Does not cause sterility in males, swelling very painful.
     E. CNS complications - asceptic meningitis, but full recovery, rarely encephalitis.
     F. Vaccine - live virus vaccine (MMR), (Jeryl Lynn strain) prolonged immunity as far as we
     know.
     G. The CDC WEB page for mumps:
         http://www.cdc.gov/nip/diseases/mumps/default.htm
        1. Vaccine - part of MMR vaccine, Mumps component is a live attenuated virus, confers
            prolonged immunity as far as we know.
        2. Discussion of the CDC recommendations and vaccine policy.
        http://www.cdc.gov/mmwr/preview/mmwrhtml/00001194.htm
IV. Parainfluenza virus infections
    A. Four serotypes, host range limited to humans, infections limited to respiratory tract,
       generally non-systemic and viremia rare.
    B. Causes cold-like symptoms, bronchitis and croup (serotypes 1 and 2). Infections of
       children common.
    C. Immunity following infection short-lived. Individuals subject to re-infection.
    D. Candidate vaccines are in various stages of clinical trials.
    E. A nice CDC summary: http://www.cdc.gov/ncidod/dvrd/revb

V. Respiratory syncytial virus infection
   A. Host range limited to humans, contagion period precedes symptoms and may occur in
   absence of symptoms.
   B. Localized infections of respiratory tract, no viremia and no systemic infections.
   C. Transmission - hand to nose contact, usually in the winter months, replication restricted to
   lower respiratory tract.
   D. Disease – bronchiolitis due to host immune response, particularly severe in infants,
   resembles asthma and blocks airways. Unusual in that severe infection occurs in first year in
   the face of maternal antibody. Also causes pneumonia.
   E. The Drug ribavarin reduces severity of symptoms.
   F. Infection in adults cold-like symptoms, immunity to natural infection not good, can get
   reinfection.
   G. No vaccine and in fact maternal antibody does not protect infants, natural infection does
   not prevent re-infection and improper vaccination increases severity of disease.
   H. Current status of RSV vaccines.
       1. Englund J, et al. Maternal immunization against viral disease. Vaccine. 1998 Aug;
       16(14-15): 1456-1463.
       2. Crowe JE Jr. Immune responses of infants to infection with respiratory viruses and live
       attenuated respiratory virus candidate vaccines. Vaccine. 1998 Aug; 16(14-15): 1423-
       1432.
   I. The CDC summary of RSV:
       http://www.cdc.gov/ncidod/dvrd/revb/respiratory/rsvfeat.htm

VI. Summary of unique features
      1. Large virion consisting of a negative sense single stranded RNA genome in a helical
         nucleocapsid surrounded by an envelope containing a viral attachment protein and a
         fusion glycoprotein (F)
      2. The three genera can be distinguished by the activities of the viral attachment protein:
         HN of paramyxovirus has hemagglutinin and neuraminidase activity; H of
         morbillivirus has hemagglutinin activity only; G of pneumovirus lacks both these
         activities.
      3. Virus replicates in the cytoplasm.
      4. Virions penetrate the cell by pH independent fusion with the plasma membrane and
         exits by budding from the plasma membrane.
      5. Viruses induce cell-cell-fusion via F protein, causing multinucleated giant cells.
      6. Paramyxoviridae are transmitted in respiratory droplets and initiate infection in the
         respiratory tract.
      7. Cell-mediated immunity causes many of the symptoms but is essential for control of
           the infection.
       8. Measles and mumps produce a viremia and a generalized infection; RSV and
       parainfluenza viruses produce only respiratory infection.

VII.   References - Chapter 55 in 4th edition of Murray, Rosenthal, Kobayashi and Pfaller
       AMedical Microbiology@