Activation of DNA Damage Response Induced by the Kaposi's Sarcoma-Associated Herpes Virus.
The human herpes virus 8 (HHV-8), also known as Kaposi sarcoma-associated herpes virus (KSHV), can infect endothelial cells often leading to cell transformation and to the development of tumors, namely Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and the plasmablastic variant of multicentric Castleman's disease. KSHV is prevalent in areas such as sub-Saharan Africa and the Mediterranean region presenting distinct genotypes, which appear to be associated with differences in disease manifestation, according to geographical areas. In infected cells, KSHV persists in a latent episomal form. However, in a limited number of cells, it undergoes spontaneous lytic reactivation to ensure the production of new virions. During both the latent and the lytic cycle, KSHV is programmed to express genes which selectively modulate the DNA damage response (DDR) through the activation of the ataxia telangiectasia mutated (ATM) pathway and by phosphorylating factors associated with the DDR, including the major tumor suppressor protein p53 tumor suppressor p53. This review will focus on the interplay between the KSHV and the DDR response pathway throughout the viral lifecycle, exploring the putative molecular mechanism/s that may contribute to malignant transformation of host cells.
Clinical Pathology and Microbiology Department, San Gallicano Institute, IRCCS, Rome 00144, Italy. e.didomenico@ifo.it.
Enea Gino
EG
Di Domenico
Infectious Disease Consultant, San Gallicano Institute, IRCCS, Rome 00144, Italy. toma@ifo.it.
Luigi
L
Toma
Clinical Pathology and Microbiology Department, San Gallicano Institute, IRCCS, Rome 00144, Italy. bordignon@ifo.it.
Valentina
V
Bordignon
Clinical Pathology and Microbiology Department, San Gallicano Institute, IRCCS, Rome 00144, Italy. trento@ifo.it.
Elisabetta
E
Trento
Clinical Pathology and Microbiology Department, San Gallicano Institute, IRCCS, Rome 00144, Italy. dagosto@ifo.it.
Giovanna
G
D'Agosto
Clinical Pathology and Microbiology Department, San Gallicano Institute, IRCCS, Rome 00144, Italy. cordiali-fei@ifo.it.
Paola
P
Cordiali-Fei
Clinical Pathology and Microbiology Department, San Gallicano Institute, IRCCS, Rome 00144, Italy. ensoli@ifo.it.
Fabrizio
F
Ensoli
D000818:Animals; D002472:Cell Transformation, Viral / Q000235:genetics; D004249:DNA Damage; D006566:Herpesviridae Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000378:metabolism / Q000821:virology; D015398:Signal Transduction; D014775:Virus Activation / Q000235:genetics; D017735:Virus Latency / Q000235:genetics; D014779:Virus Replication
DNA damage response; cancer; kaposi; sarcoma; skin; tumor