On entering sensory ganglia,herpes simplex viruses 1(HSV-1)establishes a latent infection with the synthesis of a latency associated transcript(LAT)or initiates productive infection with expression of a set of immedia...On entering sensory ganglia,herpes simplex viruses 1(HSV-1)establishes a latent infection with the synthesis of a latency associated transcript(LAT)or initiates productive infection with expression of a set of immediate early viral proteins.The precise mechanisms how expression of a genes is suppressed during the latency are unknown.One mechanism that has been proposed is illustrated in the case of ICP0,a key immediate early viral regulatory protein.Specifically,the 2 kb LAT intron is complementary to the 30 terminal portion of ICP0 m RNA.To test the hypothesis that accumulation of LAT negatively affects the accumulation of ICP0 m RNA,we inserted a DNA fragment encoding two poly(A)sequences into LAT to early terminate LAT transcript without interrupting the complementary sequence of ICP0 transcript(named as SR1603).Comparisons of the parent(SR1601)and mutant(SR1603)HSV-1 viruses showed the following:Neurons harboring latent SR1603 virus accumulated equivalent amounts of viral DNA but higher amounts of ICP0 m RNA and lower amounts of LAT,when compared to neurons harboring the SR1601 virus.One notable difference between the two viruses is that viral RNA accumulation in explanted ganglia harboring SR1603 virus initiated significantly sooner than that in neurons harboring SR1601 virus,suggesting that ICP0 may act as an activator of viral gene expression in permissive cells.Collectively,these data suggest that increased ICP0 m RNA by suppressed LAT did not affect the establishment of latency in latently infected murine ganglia.展开更多
Herpes simplex virus type 1(HSV-1)is a common hu-man pathogen causing cold sores and even more se-rious diseases.It can establish a latent stage in sensory ganglia after primary epithelial infections,and reacti-vate i...Herpes simplex virus type 1(HSV-1)is a common hu-man pathogen causing cold sores and even more se-rious diseases.It can establish a latent stage in sensory ganglia after primary epithelial infections,and reacti-vate in response to stress or sunlight.Previous studies have demonstrated that viral immediate-early protein ICP0 plays a key role in regulating the balance between lytic and latent infection.Recently,It has been deter-mined that promyelocytic leukemia(PML)nuclear bod-ies(NBs),small nuclear sub-structures,contribute to the repression of HSV-1 infection in the absence of functional ICP0.In this review,we discuss the funda-mentals of the interaction between ICP0 and PML NBs,suggesting a potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1.展开更多
基金supported by grants from Shenzhen Overseas High-Caliber Peacock Foundation KQTD2015071414385495Shenzhen Science and Innovation Commission Project Grants JCYJ20180306173333907 to Shenzhen International Institute for Biomedical Research。
文摘On entering sensory ganglia,herpes simplex viruses 1(HSV-1)establishes a latent infection with the synthesis of a latency associated transcript(LAT)or initiates productive infection with expression of a set of immediate early viral proteins.The precise mechanisms how expression of a genes is suppressed during the latency are unknown.One mechanism that has been proposed is illustrated in the case of ICP0,a key immediate early viral regulatory protein.Specifically,the 2 kb LAT intron is complementary to the 30 terminal portion of ICP0 m RNA.To test the hypothesis that accumulation of LAT negatively affects the accumulation of ICP0 m RNA,we inserted a DNA fragment encoding two poly(A)sequences into LAT to early terminate LAT transcript without interrupting the complementary sequence of ICP0 transcript(named as SR1603).Comparisons of the parent(SR1601)and mutant(SR1603)HSV-1 viruses showed the following:Neurons harboring latent SR1603 virus accumulated equivalent amounts of viral DNA but higher amounts of ICP0 m RNA and lower amounts of LAT,when compared to neurons harboring the SR1601 virus.One notable difference between the two viruses is that viral RNA accumulation in explanted ganglia harboring SR1603 virus initiated significantly sooner than that in neurons harboring SR1601 virus,suggesting that ICP0 may act as an activator of viral gene expression in permissive cells.Collectively,these data suggest that increased ICP0 m RNA by suppressed LAT did not affect the establishment of latency in latently infected murine ganglia.
基金supported by grants from the State Key Development Program for Basic Research of China(973 Program)(Grant Nos.2010CB530105 and 2011CB504802)The Startup Fund of the 100 Talents Program from the Chinese Academy of Sciences(No.20072020-141)National Natural Science Foundation of China(Grant Nos.30870120,81171584,81101263,and 81000736)。
文摘Herpes simplex virus type 1(HSV-1)is a common hu-man pathogen causing cold sores and even more se-rious diseases.It can establish a latent stage in sensory ganglia after primary epithelial infections,and reacti-vate in response to stress or sunlight.Previous studies have demonstrated that viral immediate-early protein ICP0 plays a key role in regulating the balance between lytic and latent infection.Recently,It has been deter-mined that promyelocytic leukemia(PML)nuclear bod-ies(NBs),small nuclear sub-structures,contribute to the repression of HSV-1 infection in the absence of functional ICP0.In this review,we discuss the funda-mentals of the interaction between ICP0 and PML NBs,suggesting a potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1.
