Lusso Paolo, Crowley Richard W, Malnati Mauro S, Di Serio Clelia, Ponzoni Maurilio, Biancotto Angelique, Markham Phillip D, Gallo Robert C
Unit of Human Virology, San Raffaele Scientific Institute, 20132 Milan, Italy.
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5067-72. doi: 10.1073/pnas.0700929104. Epub 2007 Mar 14.
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.
虽然人类免疫缺陷病毒（HIV）是获得性免疫缺陷综合征（AIDS）的必要且充分致病因子，但遗传和环境因素显著影响疾病进展的速度。临床和实验证据表明，人疱疹病毒6A（HHV-6A），一种具有细胞病变效应的嗜T淋巴细胞DNA病毒，与HIV-1协同促进AIDS的进展。在本研究中，我们调查了HHV-6A合并感染对食蟹猴（Macaca nemestrina）中猴免疫缺陷病毒（SIV）疾病进展的影响。接种HHV-6A导致血浆病毒血症迅速出现，伴有短暂的临床表现，随后发生抗体血清转化，表明该灵长类动物物种易受HHV-6A感染。虽然单独感染HHV-6A的动物未表现出任何长期的临床和免疫后遗症，但在所有接种SIV的猕猴中均观察到CD4(+) T细胞逐渐减少。然而，HHV-6A合并感染显著加速了进展为全面AIDS的进程。双重感染动物中疾病的快速发展以CD4(+)和CD8(+) T细胞的早期耗竭为先兆。这些结果提供了体内证据，表明HHV-6A可能是AIDS进展中的一个促进因素。
