Herpes simplex virus type 1 serum neutralizing antibody titers increase during latency in rabbits latently infected with latency-associated transcript (LAT)-positive but not LAT-negative viruses
Gc. Perng et al., Herpes simplex virus type 1 serum neutralizing antibody titers increase during latency in rabbits latently infected with latency-associated transcript (LAT)-positive but not LAT-negative viruses, J VIROLOGY, 73(11), 1999, pp. 9669-9672
The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT)
gene is essential for efficient spontaneous reactivation in the rabbit ocu
lar model of HSV-1 latency and reactivation. LAT is also the only viral gen
e abundantly expressed during latency. Rabbits were ocularly infected with
the wild-type HSV-1 strain McKrae or the McKrae-derived LAT null mutant dLA
T2903. Serum neutralizing antibody titers were determined at various times
during acute and latent infection. The neutralizing antibody titers induced
by both viruses increased and were similar throughout the first 45 days af
ter infection (P > 0.05). However, by day 59 postinfection (approximately 3
1 to 45 days after latency had been established), the neutralizing antibody
titers induced by wild-type virus and dLAT2903 diverged significantly (P =
0.0005). The dLAT2903-induced neutralizing antibody titers decreased, whil
e the wild-type virus-induced neutralizing antibody titers continued to inc
rease. A rescuant of dLAT2903, in which spontaneous reactivation was fully
restored, induced wild-type neutralizing antibody levels on day 59 postinfe
ction, A second LAT mutant with impaired spontaneous reactivation had neutr
alizing antibody revels comparable to those of dLAT2903. In contrast to the
results obtained in rabbits, in mice, neutralizing antibody titers did not
increase over time during latency with any of the viruses. Since LAT is ex
pressed in both rabbits and mice during latency, the difference in neutrali
zing antibody titers between these animals is unlikely to be due to express
ion of a LAT protein during latency. In contrast, LAT-positive (LAT(+)), bu
t not LAT-negative (LAT(-)), viruses undergo efficient spontaneous reactiva
tion in rabbits, while neither LAT(+) nor LAT(-) viruses undergo efficient
spontaneous reactivation in mice. Thus, the increase in neutralizing antibo
dy titers in rabbits latently infected with LAT(+) viruses may have been du
e to continued restimulation of the immune system by spontaneously reactiva
ting virus.