TY - JOUR
T1 - Human herpesvirus 6A accelerates AIDS progression in macaques
AU - Lusso, Paolo
AU - Crowley, Richard W.
AU - Malnati, Mauro S.
AU - Di Serio, Clelia
AU - Ponzoni, Maurilio
AU - Biancotto, Angelique
AU - Markham, Phillip D.
AU - Gallo, Robert C.
PY - 2007/3/20
Y1 - 2007/3/20
N2 - Although HIV is the necessary and sufficient causative agent of AIDS, genetic and environmental factors markedly influence the pace of disease progression. Clinical and experimental evidence suggests that human herpesvirus 6A (HHV-6A), a cytopathic T-lymphotropic DNA virus, fosters the progression to AIDS in synergy with HIV-1. In this study, we investigated the effect of coinfection with HHV-6A on the progression of simian immunodeficiency virus (SIV) disease in pig-tailed macaques (Macaca nemestrina). Inoculation of HHV-6A resulted in a rapid appearance of plasma viremia associated with transient clinical manifestations and followed by antibody seroconversion, indicating that this primate species is susceptible to HHV-6A infection. Whereas animals infected with HHV-6A alone did not show any long-term clinical and immunological sequelae, a progressive loss of CD4+ T cells was observed in all of the macaques inoculated with SIV. However, progression to full-blown AIDS was dramatically accelerated by coinfection with HHV-6A. Rapid disease development in dually infected animals was heralded by an early depletion of both CD4 + and CD8+ T cells. These results provide in vivo evidence that HHV-6A may act as a promoting factor in AIDS progression.
AB - Although HIV is the necessary and sufficient causative agent of AIDS, genetic and environmental factors markedly influence the pace of disease progression. Clinical and experimental evidence suggests that human herpesvirus 6A (HHV-6A), a cytopathic T-lymphotropic DNA virus, fosters the progression to AIDS in synergy with HIV-1. In this study, we investigated the effect of coinfection with HHV-6A on the progression of simian immunodeficiency virus (SIV) disease in pig-tailed macaques (Macaca nemestrina). Inoculation of HHV-6A resulted in a rapid appearance of plasma viremia associated with transient clinical manifestations and followed by antibody seroconversion, indicating that this primate species is susceptible to HHV-6A infection. Whereas animals infected with HHV-6A alone did not show any long-term clinical and immunological sequelae, a progressive loss of CD4+ T cells was observed in all of the macaques inoculated with SIV. However, progression to full-blown AIDS was dramatically accelerated by coinfection with HHV-6A. Rapid disease development in dually infected animals was heralded by an early depletion of both CD4 + and CD8+ T cells. These results provide in vivo evidence that HHV-6A may act as a promoting factor in AIDS progression.
KW - Animal models
KW - Herpesviruses
KW - Simian immunodeficiency virus
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U2 - 10.1073/pnas.0700929104
DO - 10.1073/pnas.0700929104
M3 - Article
C2 - 17360322
AN - SCOPUS:34247554223
VL - 104
SP - 5067
EP - 5072
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 12
ER -