Selected Reviews of the Literature

Abstract

sent a difficult therapeutic problem. Paradoxically, most patients who are plagued with recurrent herpes tiave high titers of specific antibody against the herpes virus. Yet almost any stress situation, whether trauma, respiratory infection, or sunburn, may precipitate an exacerbation, usually at the site or sites previously involved. Several theories have been advanced to explain re¬ current herpes simplex in man. That each recurrence represents a reinfection seems unlikely. A second proposal is that multiple antigenic strains of the herpes virus exist. Mutant strains are reported to arise in tissue culture when the antibody is present (Amer J Hyg 70:208, 1959). The mutant strain possessed an increased infectivity in culture and was not affected by the presence of the antibody. A third hypothesis is that tissue injury which in¬ volves infected cells results in intracellular edema with consequent local dilution of the specific antibody. The herpes virus particles are released from the injured carrier cells and are able to spread to nearby cells, unmolested by the dilute concentrations of antibody. In tissue culture, however, even adequate amounts of the specific antibody have proved ineffective to stop the local spread of the virus through the culture (Arch Derm 79:86, 1959; Arch Ges Virusforsch 11 :86, 1961). Some inhibition of viral spread occurred if the anti¬ body was added to the tissue culture early in the experiment (/ Immunol 74:236, 1955), hut if the anti¬ body was added after 20 hours, it was inefficacious and the entire culture became infected. In a recent study, Huang and Wagner (Proc Soc Exp Biol Med 116: 863, 1964) determined that viral penetration into culture cells was complete within seven minutes at 37 C. They believed that after this brief time, the addition of antibody had no inhibiting or inactivatng effect on the subsequent infectivity of the virus. Other authors have postulated that the virus is in¬ accessible (intracellular?) to the antibody, or that it is present in a morphologic form which cannot be neutralized by the specific antibody. Two morphologic forms of the herpes virus have been demonstrated by ultramicroscopic techniques : the enveloped particle and the naked particle. The pro¬ tein envelope is believed to be derived from host cell material and therefore consists largely of host cell constituents. Enveloped viral particles are more readily absorbed on host cells, although some naked particles do absorb to susceptible cells. Some authors have be¬ lieved the envelope is essential to virus particle in¬ fectivity while other authors disagree with this point of view. In an attempt to explore this question (Proc Soc Exp Biol Med 115:814, 1964), crude herpes virus sus¬ pensions were fractionated into enveloped and naked virus particles by density gradient sedimentation with cesium chloride. Particles without envelopes were found to be almost noninfective, whereas enveloped particles were highly infectious. The author concluded that the protein envelope was necessary for herpes virus particle infectivity. The envelope may serve as a protective physical barrier from inactivation of the virus by destructive enzymes ; it may maintain the internal milieu of the virus particle by the preservation of essential compo¬ nents within the virus. Since the protein envelope of the virus particle arises from host cell membranes, it conceivably could protect the inner viral particle from contact with the antibody, prevent the recognition of the viral DNA as foreign, and permit passage of the virus unmolested from cell to cell. Enveloped particles would thus be more infectious by reason of their immunity from interference from the antibody. The author pointed out that herpes simplex is the only group of virus with cubic symmetry known which possess an envelope derived from the host cell mem¬ branes. Further, the herpes virus is, to the knowledge of this reviewer, the only virus with which recurrent acute episodes in the skin of man are not uncommon. Whether these two observations have a unique and significant relationship awaits confirmation.