Anders Vahlne

Involvement of glycoprotein C (gC) in adsorption of herpes simplex virus type 1 (HSV-1) to the cell

SummaryResults demonstrating involvement of glycoprotein C (gC) of herpes simplex type 1 virus (HSV-1) in attachment of the virus to the cell are presented. Monoclonal antibodies against gC-1 inhibited adsorption of gC+-strains. The gC−-mutant, MP, attached to cells but at a reduced rate. Attachment of the MP-mutant was unaffected by presence of anti-gC-1 antibody. Purified truncated gC-1 adsorbed to cells at a rate essentially the same as that of gC+-virus. Glycoprotein C-1 pretreated with heparin did not adsorb to cells. The results are compatible with a suggested role for gC in HSV attachment.

Herpes simplex virus infection of mouse neuroblastoma cells.

Summary Herpes simplex virus infection was studied in in vitro cultured mouse neuroblastoma (C 1300) cells displaying many properties characteristic of differentiated neurons. High multiplicity of infection caused a cytocidal type of infection. At a low multiplicity of infection, cultures persistently or only occasionally releasing virus into the culture fluid were established. These cultures have been subcultured more than 40 times. C 1300 Cells produced hundred- to thousand-fold less HSV per cell than a number of other cell cultures of murine, simian, or human origin. About 1% of the C 1300 cells in a culture persistently releasing virus was found to carry HSV-induced antigens. Since HSV antiserum added to the persistently infected cultures efficiently cleared cultures of infective virus, cell-to-cell spread of virus seemed of minor importance. This work was supported by the Swedish Medical Research Council (Project No. 4514).

Herpes simplex virus latency in a hyperresistant clone of mouse neuroblastoma (Cl300) cells

SummaryHerpes simplex virus (HSV) hyperresistant neuroblastoma cells (clone Cl300 RII) were latently infected with HSV-1 if cultured in presence of HSV-neutralizing antibody for one or two passages after infection and then passaged further without antibody. By superinfecting HSV-1 latently infected Cl300 RII cells with HSV-2, progeny virus with HSV-1 characteristics was regularly rescued. Such retrieval of HSV-1 decreased with passage of the latently infected cells.

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

SummaryThe 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 supported 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.

Persistent reactivable latent herpes simplex virus infection in trigeminal ganglia of mice treated with antiviral drugs

SummaryLatent reactivable infection was established with HSV in mouse trigeminal ganglion. A number of antiviral drugs (IUDR, acycloguanosine, Ara-A, PAA and PFA), effective against acute CNS infection with HSV, failed to influence the latent infection once established. Neither lipophilic properties of PFA-derivatives nor the combination of Ara-A and acyloguanosine improved the drug-effects on HSV latency.

Amplification of herpes simplex virus resistance in mouse neuroblastoma (Cl300) cells

SummaryClones of mouse neuroblastoma (Cl300) cells with increased resistance to herpes simplex virus (HSV) were obtained among survivors after prolonged exposure of partially HSV resistent Cl300 cells to successively increasing multiplicities of infection (MOI) of HSV. The increased restrictedness to HSV of these Cl300 R clones (Cl300 RI and Cl300 RII) as compared to the parental Cl300 cells was demonstrated by a tolerance to higher MOIs of HSV, jugded by the appearance of cytopathic effects; by lower yields of progeny virus; and by higher activities of a non-interferon HSV inhibitor. Morphological appearance, cellular growth rate as well as HSV adsorptive capacity of the Cl300 R cells did not differ from that of Cl300 cells. Neither was virus penetration affected. These neuroblastoma Cl300 R cells, demonstrating an amplified resistance to HSV, might serve useful in studies on the regulation of virus replication in HSV latency establishment in neurons.

The Herpes Simplex Virus Infection of the Rat Sensory Neuron

Conditions with confusion, anxiety, excitation, or aggression may be the earliest and the most prominent symptoms of an acute viral CNS infection. Various kinds of personality changes including a more or less severe mental deterioration may remain as sequelae after a virus infection of the brain. Undoubtedly, observations like these have kept alive the interest in virus infections as potential triggers of psychotic disorders. Of all the possible viral candidates, the herpes viruses are perhaps those that have attracted most of the attention because of their neurotropic properties, the capacity to induce reactivatable latent infections, and a ubiquitous occurrence.