Hampar, Berge (National Institute of Dental Research, Bethesda, Md.). Persistent cyclic herpes simplex virus infection in vitro. II. Localization of virus, degree of cell destruction, and mechanisms of virus transmission. J. Bacteriol. 91:1959-1964. 1966. The localization of virus, degree of cell destruction, and mechanisms of virus transmission in persistent herpes simplex virus-infected cultures were studied. The major fraction of infectious virus was associated with the medium and a minor fraction was associated with the attached cells. Virus in the medium was further separable into a sedimentable (cellular) fraction and a nonsedimentable (extracellular) fraction. The sedimentable fraction was comprised of cellular debris, most of which appeared to contain viral antigen, and intact cells of which less than 10% contained infectious virus. Cell destruction during the cycle involved more than 99.9% of the maximal number of cells present. Infection could be transmitted by extracellular virus, cell-to-cell transfer, and reattachment of infectious cellular material. The results indicated that transmission by reattachment was probably mediated through the cellular debris rather than the intact cells.

Antigens↗

PubMed1966

Persistent cyclic herpes simplex virus infection in vitro. 3. Asynchrony in the progression of infection and cell regrowth.

Hampar, Berge (National Institute of Dental Research, Bethesda, Md.). Persistent cyclic herpes simplex virus infection in vitro. III. Asynchrony in the progression of infection and cell regrowth. J. Bacteriol. 91:1965-1970. 1966.-The progression of virus-induced cytopathic effects (CPE) and virus synthesis was studied in localized areas of Chinese hamster cell cultures persistently infected with herpes simplex virus (HSV). CPE was initially evidenced by the presence of small multinucleated giant cells, followed by expanding plaquelike lesions with an occasional uninfected cell remaining within the infected areas. Cell detachment rapidly followed the appearance of viral antigen in infected cells. The surviving cells which proliferated to re-establish the cell sheet arose from two sources. The first was from viable cells which remained attached after expansion of localized areas of CPE, and the second was from reattachment of viable cells in the medium. CPE in localized areas was initiated at various times during the cycle irrespective of the virus titer in the medium. Cell regrowth in some areas and CPE in other areas occurred simultaneously throughout the cycle in an asynchronous fashion. Consequently, during periods of rising virus titers, most areas showed CPE while few areas displayed cell regrowth. As the virus titers declined, more areas showed cell regrowth and fewer areas displayed new cycles of CPE. CPE in localized areas was not initiated until cell regrowth had occurred. It is proposed that the proliferating cells were temporarily resistant to HSV infection, and that this resistance was ultimately lost in their progeny cells.

Antigens↗

PubMed1966

Persistent cyclic herpes simplex virus infection in vitro. IV. Changes in the severity of the infections in the presence of antibody.

Hampar, Berge (National Institute of Dental Research, Bethesda, Md.). Persistent cyclic herpes simplex virus infection in vitro. IV. Changes in the severity of the infections in the presence of antibody. J. Bacteriol. 92:1741-1747. 1966.-The severity of persistent herpes simplex virus (HSV) infections maintained in the presence of viral antibody (AB) changed with time. These changes could be divided into three distinct phases during which the severity of the infections were maintained at low (phase 1), high (phase 2), and intermediate (phase 3) levels. Paralleling these changes was the appearance in the cultures of a new HSV variant which induced the formation of giant cells. The changes in the severity of the infections were attributable to three factors. The first was the presence in the cultures of virus-resistant cells. The second was the suppressive effects due to virus neutralization by the AB. The third was the inherent properties of each HSV variant which determined the amount of virus remaining in an infectious form in the presence of AB. Finally, the period of "exacerbation" in vitro (phase 2) was compared with recurrent episodes in human herpes infection.

Animals↗

PubMed1965

Persistent Herpes Simplex Virus Infection In Vitro with Cycles of Cell Destruction and Regrowth.

Hampar, Berge (National Institute of Dental Research, Bethesda, Md.), and Mary Lou Copeland. Persistent herpes simplex virus infection in vitro with cycles of cell destruction and regrowth. J. Bacteriol. 90:205-212. 1965.-The susceptibility of two Chinese hamster cell lines to herpes simplex virus (HSV) was studied from the time of their initiation through successive subcultures. The cells' susceptibility to the cytocidal effects of HSV decreased as the number of cell passages increased. During the early cell passages, the decrease in cell susceptibility to HSV was characterized by an increased time after infection for complete cell destruction to occur, with a concomitant increase in the period when virus could be recovered from supernatant fluids. This was followed by a number of cell passages during which persistent HSV infections were established. The persistent infections were characterized by (i) cycles of virus synthesis and cell destruction followed by regrowth of the cells, (ii) initiation and maintenance under conditions optimal for cell growth in the absence of antibody, (iii) the cells' ability to be passaged while still maintaining their cycling patterns, (iv) a relationship between virus synthesis and cell proliferation, and (v) inability of long-term treatment with antibody to "cure" the persistent infections. The unique characteristics of this HSV infection were compared with other persistent in vitro viral infections.

Journal Article↗