Langley R J, Prince G A, Ginsberg H S
Virion Systems, Inc., 9610 Medical Center Drive, Rockville, MD 20850, USA.
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14355-60. doi: 10.1073/pnas.95.24.14355.
Cotton rats (Sigmodon hispidus and S. fulviventer) are susceptible to many viruses that infect humans (e.g., poliovirus, respiratory syncytial virus, influenza virus, adenovirus, and parainfluenza virus) and have been influential in developing therapeutic clinical intervention strategies for many viral infections of man. This study set out to determine whether cotton rats are susceptible to infection with HIV type 1 (HIV-1). Results indicate that HIV-1 does infect the cotton rat and S. fulviventer is more susceptible than S. hispidus. The virus was passaged from animal to animal for a total of three serial passages; but HIV replicated poorly in vivo, was only detectable as proviral DNA, and never exceeded one provirus per 1.8 x 10(5) cotton rat peripheral blood mononuclear cells. Infection induced a distinct and characteristic anti-HIV antibody response that, in some animals, included neutralizing antibodies, recognized all of the major HIV-1 antigens and the antibodies lasted out to 52 wk post-infection. Neonate S. fulviventer were not more susceptible to infection than adults. In vitro culture studies produced indirect evidence of viral replication by detection of viral gag gene RNA in reverse transcriptase-PCR assays on viral culture supernatants. Collectively, these results indicate that HIV-1 can replicate in a nontransgenic rodent and that this system may have potential as an animal model for HIV-1 infection if viral replication rates can be improved in vivo.
棉鼠(刚毛棉鼠和黄腹棉鼠)对许多感染人类的病毒敏感(如脊髓灰质炎病毒、呼吸道合胞病毒、流感病毒、腺病毒和副流感病毒),并且在为人类的许多病毒感染制定治疗性临床干预策略方面发挥了重要作用。本研究旨在确定棉鼠是否易感染1型人类免疫缺陷病毒(HIV-1)。结果表明,HIV-1确实能感染棉鼠,且黄腹棉鼠比刚毛棉鼠更易感染。该病毒在动物之间连续传代了三次;但HIV在体内复制不佳,仅能检测到作为前病毒DNA的形式,并且每1.8×10⁵个棉鼠外周血单个核细胞中前病毒数量从未超过一个。感染诱导了一种独特且具有特征性的抗HIV抗体反应,在一些动物中,包括中和抗体,可识别所有主要的HIV-1抗原,且抗体在感染后可持续52周。新生黄腹棉鼠并不比成年棉鼠更易感染。体外培养研究通过在病毒培养上清液的逆转录聚合酶链反应检测病毒gag基因RNA,间接证明了病毒的复制。总体而言,这些结果表明HIV-1可在非转基因啮齿动物中复制,如果能提高其在体内的病毒复制率,该系统可能有潜力作为HIV-1感染的动物模型。