Induction of human immunodeficiency virus 1 replication by human herpesvirus 8.
BACKGROUND
Human immunodeficiency virus 1 (HIV-1)-infected individuals are commonly infected with herpesviruses, including cytomegalovirus, herpes simplex virus, varicella-zoster virus, and human herpesvirus 8 (HHV-8, also known as Kaposi sarcoma-associated herpesvirus [KSHV]). Previous studies have demonstrated that coinfection with herpesviruses can modulate HIV-1 replication. This can occur either through direct interaction between the 2 viruses or through secondary effects resulting from the release of cellular factors in response to infection.


OBJECTIVE
To investigate HIV-1 replication in the presence and absence of HHV-8.


METHODS
HIV-1 replication was analyzed following culture of HIV-1-infected CD4(+) T cells in the presence of HHV-8 infected B-cell lines or control, uninfected B-cell lines. To confirm and extend the results of these in vitro studies, HIV-1-infected T cells were injected into human skin transplanted onto severe combined immunodeficient mice. The human skin was also injected with purified HHV-8 or phosphate-buffered saline as a control and HIV replication measured in biopsy specimens taken 5 to 8 days later.


CONCLUSIONS
The results demonstrated a significant increase in HIV-1 replication in the presence of HHV-8 in both the in vitro and in vivo model systems. Although the mechanism responsible for HHV-8 induction of HIV-1 replication remains to be identified, the results indicate that these 2 viruses may interact at the molecular level in coinfected patients, resulting in increased HIV-1 viral load.
Mercader
M
M
Department of Pathology and Skin Cancer Research Laboratories, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, USA.
Nickoloff
B J
BJ
Foreman
K E
KE
D000818:Animals; D001402:B-Lymphocytes / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation / Q000821:virology; D002460:Cell Line; D015658:HIV Infections / Q000150:complications / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006566:Herpesviridae Infections / Q000150:complications / Q000821:virology; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D016038:Skin Transplantation; D015163:Superinfection / Q000821:virology; D014183:Transplantation, Heterologous; D014779:Virus Replication / Q000502:physiology*