Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 RTA reactivates murine gammaherpesvirus 68 from latency.
Murine gammaherpesvirus 68 (MHV-68), Kaposi's sarcoma-associated herpesvirus (HHV-8), and Epstein-Barr virus (EBV) are all members of the gammaherpesvirus family, characterized by their ability to establish latency in lymphocytes. The RTA protein, conserved in all gammaherpesviruses, is known to play a critical role in reactivation from latency. Here we report that HHV-8 RTA, not EBV RTA, was able to induce MHV-68 lytic viral proteins and DNA replication and processing and produce viable MHV-68 virions from latently infected cells at levels similar to those for MHV-68 RTA. HHV-8 RTA was also able to activate two MHV-68 lytic promoters, whereas EBV RTA was not. In order to define the domains of RTA responsible for their functional differences in viral promoter activation and initiation of the MHV-68 lytic cycle, chimeric RTA proteins were constructed by exchanging the N-terminal and C-terminal domains of the RTA proteins. Our data suggest that the species specificity of MHV-68 RTA resides in the N-terminal DNA binding domain.
Rickabaugh
Tammy M
TM
Department of Molecular and Medical Pharmacology, University of California at Los Angeles, Los Angeles, CA 90095-1735, USA.
Brown
Helen J
HJ
Wu
Ting-Ting
TT
Song
Moon Jung
MJ
Hwang
Seungmin
S
Deng
Hongyu
H
Mitsouras
Katherine
K
Sun
Ren
R
D000818:Animals; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D018144:Rhadinovirus / Q000235:genetics* / Q000502:physiology*; D013045:Species Specificity; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D014775:Virus Activation / Q000235:genetics / Q000502:physiology; D017735:Virus Latency / Q000235:genetics / Q000502:physiology
C068382:BRLF1 protein, Human herpesvirus 4; D017874:Immediate-Early Proteins; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014764:Viral Proteins