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Current Developments in Virology Scientists from around the world met at WHO Headquarters in Geneva not long ago to review current knowledge on the viral diseases and to draw up a program for the next decade aimed at dealing with the public health problems that these diseases cause. It was determined that attention should be given first to working out public health procedures for those diseases which affect large segments of the population and for which immuniza- tion is practical. The next priority was assigned to diseases that have implications for international health but for which vaccines are not yet available. A third order of priority was established for diseases that still require much basic research and whose continued study is urged. The Bulletin is publishing selections from this meeting’s short working papers in three installments. Those dealing with the first two priority areas were published in numbers 3 and 4 of 1976. The four selections presented here deal with the third area-diseases requiring considerable further study. THE HERPESVIRUS GROUP’ J. L. Mehick* Several agents in the herpesviTus group are known to infect man. They cause a wide variety of conditions, ranging from coldrores to chickenpox and shingles. At the same time a number of the herpesviruses have been linked with malignant diseases in both lower animals and man. At least 25 viruses have been placed in Epstein-Barr (EB) virus, and cytomegalo- the herpesvirus group on the basis of their virus infect man. Types 1 and 2 virus are DNA genome and common architecture. readily found extracellularly in the fluid Within the group, herpes simplex virus phase of tissue cultures, but the other types 1 and 2, varicella-zoster virus, members of the group are more firmly as- sociated with the cell. Although varicella and zoster strains have been grown in a lWorking paper, WHO Scientific Group on Virus number of tissue cultures, they have not Diseases (Geneva, 1-5 September 1975). yet regularly been obtained free in the ZDistinguished Service Professor, Department of Virology and Epidemiology, Baylor College of Medi- fluid phase (except when grown in cells cine, Houston, Texas, U.S.A. from human thyroid tissues). The EB 153 154 PAHO BULLETIN l Vol. XI, No.~- 2, 1977 herpesvirus appears to replicate only in herpes labialis). The primary infection in human lymphoid cell cultures. most individuals is clinically inapparent After inactivation with ultraviolet irra- and thus often not recognized. However, diation, herpesvirus types 1 and 2 can still antibody production invariably accompa- cause oncogenic transformation of hamster nies the infection. The recurrent attacks cells. Functional viral genetic information often follow nonspecific stimuli such as is found to be present in the tumor cells. exposure to excessive sunlight, fever accom- Herpesviruses that infect lower animals panying certain infections, menstruation, are the B virus of Old World monkeys; or emotional stress. herpesviruses saimiri, aotus, and ateles; Herfiesvirus ty#e 1. The clinical entities marmoset herpesvirus of New World mon- attributable to herpesvirus type 1 include keys; pseudorabies virus of pigs; virus III the following: acute herpetic gingivostoma- of rabbi’ts; infectious bovine rhinotracheitis titis (aphthous stomatitis, Vincent’s stoma- virus; equine rhinopneumonitis (equine titis), eczema herpeticum (Kaposi’s varicel- abortion) virus; canine herpesvirus; infec- liform eruption), keratoconjunctivitis, tious laryngotracheitis virus of fowl; and meningoencephalitis, herpes simplex (her- cytomegaloviruses of monkeys, guinea pigs, pes febrilis, herpes labialis). mice, and other animal species. Herpes- Herpesvirus type 2. The clinical entities viruses are also known to infect cold- associated with herpesvirus type 2 include blooded animals (frogs and snakes). The genital herpes (herpes progenitalis) and widespread occurrence of herpesviruses in neonatal herpes. primates has previously been discussed in a Miscellaneous. Localized lesions of the paper by Barahona et al. (I). skin caused by types 1 or 2 may occur in Herpesviruses have also been linked with abrasions which become contaminated with malignant diseases in man and lower the virus (traumatic herpes). Mild aseptic animals: herpes simplex virus types 1 and meningitis has been attributed to the virus, 2, respectively, with labial and cervical and recurrent episodes of meningeal irrita- carcinomas of man; EB virus with Burkitt’s tion have also been observed. In most lymphoma of African children and with geographic areas patients with cervical nasopharyngeal carcinoma; Lucke virus cancer have a high frequency of type 2 with renal adenocarcinomas of the frog; antibodies. Marek’s disease virus with a lymphoma of Herpesviruses are susceptible to photo- chickens; Hinze virus with a lymphoma of inactivation when presensitized with sub- rabbits; and a number of New World stances such as neutral red or proflavine. primate herpesviruses with reticulum cell Application of these agents to active type 1 sarcomas and lymphomas in these animals. and type 2 skin lesions, followed by ade- quate exposure to light of the proper wave- Herpes Simplex Virus length and of sufficient intensity, reduces the duration of the lesions and the rate of Herpesvirus types 1 and 2 may produce recurrence. various specific clinical entities, and the infections themselves may be either pri- mary or recurrent. Primary infections Varicella-Zoster Virus which occur in persons without antibodies often result in the virus assuming a latent Varicella (chickenpox) is a mild but state in the host. Latent infections persist highly infectious disease, chiefly of chil- in persons with antibodies, and recurrent dren, characterized by a vesicular eruption infections are common (e.g. recurrent of the skin and mucous membranes. In im- VIROLOGY l Melnick l HERPESVIRUSES 155 munocompromised children it can be intrauterine or early postnatal infection severe. with cytomegalovirus. (Indigenous cyto- Zoster (shingles) is a sporadic incapaci- megaloviruses exist in several animal spe- tating disease of adults (rare in children) cies). The disease is characterized by large which is characterized by an inflammatory basophilic (or sometimes eosinophilic) intra- reaction of the posterior nerve roots and nuclear inclusions in the salivary glands, ganglia; it is accompanied by crops of lungs, liver, pancreas, kidneys, endocrine vesicles (like those of varicella) over the glands, and occasionally in the brain. Most skin served by the affected sensory nerves. fatalities occur in children under two years The varicella and zoster viruses are iden- of age. Inapparent infection is common tical agents, the two diseases being the result during childhood and adolescence. of different host responses. Previous infec- Congenital cytomegalic inclusion disease tion with varicella leaves the patient with was once believed fatal in all cases, but in enduring immunity thereto, whereas zoster fact infants with the disease may survive may occur in persons who have contracted initial infection and live for many years. A varicella at an earlier date. The latter significant proportion of unexplained mi- probably represents reactivation of a vari- crocephaly and mental retardation may be cella virus infection which has been latent caused by congenital cytomegalovirus for many years. infections. Individuals with a recent history of Patients with malignancies or immunolo- varicella or zoster infection respond to a gic defects or those undergoing immuno- herpes simplex infection with a concomi- suppressive therapy for organ transplanta- tant rise in complement-fixing antibody to tion may develop cytomegalovirus pneumo- both herpes simplex and varicella-zoster nitis, hepatitis, and occasionally general- viruses. ized disease; the relative importance of A rapid way of differentiating between primary infection versus reactivation of a vesicular lesions caused by herpesviruses latent infection in such cases remains to be (lesions due to herpes simplex or varicella- clarified. zoster viruses) and those caused by poxvi- Except in the case of congenital infec- ruses (smallpox or generalized vaccinia) is tion, the mechanism of virus transmission to examine negatively stained vesicle fluid is still unknown. Widespread infection with the electron microscope to detect the with cytomegalovirus does occur, as indi- presence of typical herpes or poxvirus cated by an increase in the rate of antibody particles. appearance with age (reaching SO per cent Gamma globulin with a high specific in individuals over 35). In addition, the antibody titer prepared from the pooled rate of virus excretion among institution- plasma of patients convalescing from herpes alized children is 10 times that among zoster (zoster immune globulin) can be children of comparable age in the popula- used to prevent or modify the development tion at large, suggesting that the virus is of illness in immunocompromised children transmitted by close contact. who have been exposed to varicella. Standard immune serum globulin is with- Epstein-Barr Herpesvirus out value because of its relatively low titer of varicella antibodies. EB virus, an antigenically distinct mem- ber of the herpes group, is believed to be Cytomegalovirus the etiologic agent of infectious mononu- Cytomegalic inclusion disease is a gener- cleosis. It has also been associated with alized infection of infants resulting from nasopharyngeal carcinoma and with Bur- 1.56 -__ -~- PAHO~--------____ BULLETIN

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