Multiplicity activation of herpes simplex virus in mouse neuroblastoma (C1300) cells

Abstract

The virus yields and number of infectious centres of HSV infected mouse neuroblastoma C1300 cells (clone 41 A3) infected at different multiplicities of infection (MOI) were found to vary more than the differences of HSV concentrations of the virus suspensions used for infection of the cells. This suggested that a C1300 cell had to be infected with more than one HSV particle in order to produce progeny virus-multiplicity activation. The greater than expected enhancement of virus production of C1300 cell cultures receiving increasing MOI of HSV was probably not due to improved virus adsorption, nor influenced by non-virus factors in the virus inoculum stimulatory for HSV replication. A hypothesis, that the block in virus replication was promoted by an inhibitor of an HSV specified regulatory protein and could be overcome by the addition of HSV DNA copies in the infected cell, was by the results of two types of experiments. Presence of phosphonoformic acid, an inhibitor of the HSV specified DNA polymerase, in the culture medium of HSV infected permissive GMK cells resulted in non-linear relationships between virus yields and MOI. An HSV temperature sensitive mutant (ts B5), defective in a late structural protein, rescued wild type HSV in C1300 cells.

Retrieval of Latent Herpes Simplex Virus Type 1 Genetic Information from Murine Trigeminal Ganglia by Superinfection with Heterotypic Virus in vivo

“…Their data suggest that multiple latent strains probably arise as a result of superinfection or simultaneous infection with more than one strain of HSV. The non-linear relationship found between inoculation dose and recovery of HSV progeny from ganglia during the acute phase of the infection (Table 3) might in fact be due to a neuronal regulated suppression of HSV in vivo and might be similar to the non-linearity of the HSV yield-inoculum relationship obtained with cultured mouse neuroblastoma cells (Vahlne et al, 1981). Lastly, superinfection with HSV-2 in the nose of mice latently infected with HSV-1 did result in activation of HSV-1 replication, as revealed by the antigenic characteristics of progeny virus and the identical restriction endonuclease cleavage patterns of progeny virus DNA and DNA of the HSV-1 strain used for establishing the latent infection.…”

“…In C1300 cells, HSV replication is suppressed if the virus dose inoculated is low. When the amount of infective virus per cell is increased, the threshold of inhibition seems to be overcome and a productive infection is obtained (Vahlne et al, 1981). We assume that a similar situation might exist for latency in vivo.…”

“…Evidence for the presence of cellular factors of importance for restriction of HSV infection in an in vitro system with C1300 neuroblastoma cells has been obtained (Vahlne et al, 1981;Nilheden et al, 1985a, b). In C1300 cells, HSV replication is suppressed if the virus dose inoculated is low.…”

Variation in resistance to herpes simplex virus type 1 of oligodendrocytes derived from inbred strains of mice

“…This phenomenon has been observed with cultured neuroblastoma cells (Vahlne et al, 1981). In this case, replication inhibition is dependent on a non-interferon host cell protein of 15K which actively inhibits virus-encoded functions (Thomas, 1985).…”

“…Other investigators suggest that natural resistance to HSV infection may also be mediated by non-immune mechanisms expressed at the level of the infected cell (Collier et al, 1983;Vahlne et al, 1981;Tenney & Morahan, 1987). Since the nervous system is the target of both acute and latent HSV infections (Roizman & Sears, 1987;Rawls, 1985), differences in the genetically determined resistance of central nervous system (CNS) cells could be important in determining the outcome of HSV infection.…”