Transcriptional and Epigenetic Regulatory Mechanisms Affecting HTLV-1 Provirus.
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with human diseases, such as adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/Tropic spastic paraparesis (HAM/TSP). As a retrovirus, its life cycle includes a step where HTLV-1 is integrated into the host genomic DNA and forms proviral DNA. In the chronic phase of the infection, HTLV‑1 is known to proliferate as a provirus via the mitotic division of the infected host cells. There are generally tens of thousands of infected clones within an infected individual. They exist not only in peripheral blood, but also in various lymphoid organs. Viral proteins encoded in HTLV-1 genome play a role in the proliferation and survival of the infected cells. As is the case with other chronic viral infections, HTLV-1 gene expression induces the activation of the host immunity against the virus. Thus, the transcription from HTLV-1 provirus needs to be controlled in order to evade the host immune surveillance. There should be a dynamic and complex regulation in vivo, where an equilibrium between viral antigen expression and host immune surveillance is achieved. The mechanisms regulating viral gene expression from the provirus are a key to understanding the persistent/latent infection with HTLV-1 and its pathogenesis. In this article, we would like to review our current understanding on this topic.
International Research Center for Medical Sciences, Center for AIDS Research, Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto 860-0811, Japan. pmiyazat@kumamoto-u.ac.jp.
Paola
P
Miyazato
International Research Center for Medical Sciences, Center for AIDS Research, Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto 860-0811, Japan. 163r5152@st.kumamoto-u.ac.jp.
Misaki
M
Matsuo
International Research Center for Medical Sciences, Center for AIDS Research, Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto 860-0811, Japan. hkatsuya@kumamoto-u.ac.jp.
Hiroo
H
Katsuya
International Research Center for Medical Sciences, Center for AIDS Research, Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto 860-0811, Japan. y-satou@kumamoto-u.ac.jp.
Yorifumi
Y
Satou
D044127:Epigenesis, Genetic; D015967:Gene Expression Regulation, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D011533:Proviruses / Q000235:genetics*; D014158:Transcription, Genetic; D017735:Virus Latency
HTLV-1 2; provirus 3; retroviral latency