Yamada, Masao

In order to elucidate the mechanism of latent infection of herpes simplex virus (HSV), reactivatable latency of three avirulent strains (SKO-1B, -GCr Miyama, SKa) of HSV type 1 was comparatively examined in a mouse latency model. The SKO-1B strain showed high rate of virus reactivation from explanted trigeminal ganglia without n-butyrate enhancement, while the other two strains showed a very low rate of virus reactivation in the absence of n-butyrate. In the presence of n-butyrate, however, the rate of the -GCr Miyama strain jumped to a comparable level with that of SKO-1B, although the rate of SKa remained at a low level. A more precise follow-up experiment changing the virus dose highlighted the difference of the ability to reactivate from the latent state between SKO-1B and -GCr Miyama. Virus titer in trigeminal ganglia during acute phase, infectivity to cell lines of neural origin, and susceptibility to acyclovir and phosphonoacetate were assayed to know the reasons for the variation in the ability of reactivatable latency among these strains. It was concluded that the reduced infectivity to neural cells, and limited ability of reactivatable latency shown by the SKa strain could mainly be attributed to the deficiency of thymidine kinase activity.</P>

Ability of two neurovirulent strains (F and +GC (LPV) Miyama) of herpes simplex virus type 1 (HSV-1) to establish and maintain reactivatable latency in trigeminal ganglia (TG) was compared after intranasal inoculation of mice. The +GC (LPV) Miyama strain showed a very low rate of virus reactivation in explant cultures of TG, while the F strain showed a high rate of reactivation. These data indicate that neurovirulent strains of HSV-1 are not always competent for reactivatable latency, although most virulent strains of HSV-1 thus far reported were competent for reactivatable latency.</P>

Epstein-Barr virus (EBV)-related herpesvirus (Si-IIA-EBV) was serially transmitted for 3 passages from rabbit to rabbit of the opposite sex by blood transfusion, which subsequently induced virus-associated rabbit lymphomas. The virus could be transmitted by transfusion with 15-20 ml of whole blood (7/7) or irradiated blood (1/6) from the EBV-related virus-infected rabbits, but there was no transmission with transfusion of cell-free plasma (0/6) from the infected rabbits. Passive anti-EBV-VCA IgG (x 20 approximately x 10) titers decreased during the first 1-2 weeks in the transfused rabbits. The virus-transmitted rabbits showed a gradual increase in antibody titers ranging from peak titers of x 640 to x 2560 after 3 weeks of transfusion. The recipient origin of malignant lymphoma that developed in the first rabbit transfused by infected blood was confirmed by chromosomal analysis. This rabbit model thus shows that EBV-related herpesvirus is serially transmissible by blood transfusion and that transmission can not be completely prevented by irradiation of blood, but removal of blood cells is the best way to prevent transmission of EBV-related virus. Therefore, this animal model provides a convenient in vivo system for studies of the prevention and therapy of transfusion-related transmission of EBV and EBV-associated lymphoproliferative diseases in immunocompromised human beings.