Erik Lycke

Neural spread of herpes simplex virus types 1 and 2 in mice after corneal or subcutaneous (footpad) inoculation

Twelve herpes simplex virus (HSV) strains, 6 of each type, were inoculated subcutaneously into the left hind foot and into the cornea of the right eye of 12-day-old Swiss albino mice. The neural spread of virus to trigeminal and spinal ganglia and to brain and spinal cord was studied by demonstration of infective virus, histology and electron microscopy. Type 1 and type 2 infections seemed to spread equally well by intra-axonal transport. Using a protein tracer (horseradish peroxidase) injected into the same site as the virus, transport of the tracer to neurons corresponding to those infected with virus was observed. The extensive destruction of CNS tissue in the transitional region of the trigeminal root where CNS and the peripheral nervous system meet is discussed with reference to the pathogenesis of HSV encephalitis.

Evidence for Herpes Simplex Virus Type-selective Receptors on Cellular Plasma Membranes

Herpes simplex virus type 1 (HSV-1) interfered with the adsorption of subsequently added homotypic but no heterotypic HSV, suggesting that the cellular receptors involved were type-selective. Both infective and u.v.-irradiated virus could block the attachment of virions to cellular surface receptors. The adsorption rate was studied by assaying non-adsorbed infective virus remaining in the fluid medium and cell-associated 3H-thymidine labelled HSV, and HSV mutants assayed in presence of phosphonoformic acid (PFA). The adsorption profiles indicated that GMK AH-1, Vero and SIRC cells all exhibited more HSV type 1-than type 2-selective receptors while HeLa S3 cells displayed more receptors with affinity for type 2 than for type 1. On HEp-2 and human embryonic lung cells HSV type 1- and type 2-selective receptors were about equally represented.

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.

Inactivation of poliomyelitis virus by formaldehyde

The course of inactivation of poliomyelitis virus by formaldehyde at 25° C was studied on tissue culture material treated by filtration through sintered glass filters. The inactivation curves deviated significantly from that of a chemical reaction of the first order.

Herpes simplex virus infection in capsaicin-treated mice

Following inoculation into the snout herpes simplex virus (HSV) spread to neurons in mouse trigeminal ganglion and subsequently to the brain. Capsaicin treatment of neonatal mice, which causes a loss of unmyelinated sensory neurons, some of which contain substance P, reduced the mortality rate of HSV-infected mice. Moreover, a lower percentage of mice survived the infection with reactivatable virus. There was also an extensive infection of glial cells proximal to the transitional zone in the trigeminal root between the peripheral and central nervous system. Distal to this zone there was an accumulation of substance P immunoreactivity in centrally directed fibres. This amplified degenerative effect on central branches of the substance P containing sensory nerves by glial infection may contribute to the deafferentiation pain syndrome following HSV infection.

Altered kinetic properties of sialyl and galactosyl transferases associated with herpes simplex virus infection of GMK and BHK cells.

Microsomal sialyl transferase and galactosyl transferase activities of herpes simplex virus-infected GMK and BHK cells were studied. Apparent Km values calculated for sialyl and galactosyl transferases differed significantly from the corresponding values of uninfected cells. Both transferases of HSV-infected cells demonstrated acceptor specificities different from those of uninfected cells. It is suggested that herpes simplex virus might influence glycosylation of proteins by modifying the glycosyl transferases of the infected cells.

Inactivation of Poliovirus by Formaldehyde. Analysis of Inactivation Curves.

As previously reported the equation logy 0 − logy=ta log (1+b t) has been found to describe the course of inactivation of poliovirus by formaldehyde. The present paper reports and discusses different methods of fitting this equation to experimental data. With the aid of the methods described data recently published byHaas et al. and byTimm et al. are analyzed. Those ofHaas et al. show an extraordinarily good fit and, thus, confirm our previous findings. On the other hand, the data ofTimm et al. do not fit the formula. Attention has been directed to certain inadequacies in the technic applied by these authors which seem to offer a plausible explanation for the discrepancies in results.

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.

Inhibition of Herpes Simplex Virus Infection in Tissue Culture by Trisodium Phosphonoformate

Summary The present report describes the in vitro effect on herpes simplex virus (HSV) replication of trisodium phosphonoformate (PFA), a drug with low toxicity and which selectively inhibits the HSV induced DNA-polymerase and thus may have potential use in the treatment of HSV infection in man. The inhibitory effect of PFA on HSV replication was strictly dose-dependent and in the presence of 0.25 mM PFA the TCID50 titers of HSV-1 and HSV-2 reference strains in green monkey kidney cells were decreased by 2 log units. The amount of virus inoculated or produced in the culture and the time for PFA-HSV interaction were factors influencing the virus inhibitory effect of PFA. None of 41 HSV-1 and 39 HSV-2 wild strains were resistant to the drug. However, passage of plaque purified HSV in the presence of 0.25 mM PFA resulted in appearance of mutants gradually more PFA resistant.

Studies of an epidemic of aseptic meningitis associated with Coxsackie and ECHO viruses. I. Virological observations.

An epidemic of aseptic meningitis was studied. Results of virus isolations and typing in two different types of tissue cultures, human embryonic lung cultures and cultures of trypsinized monkey kidney, and in baby mice indicated that the epidemic was mainly caused by ECHO virus type 6. This virus was prevalent in 57% of the cases. Coxsackie viruses were found in 13% and poliomyelitis virus type 3 in one %. In total, virus was recovered in 73%.