Bieniasz P D, Rethwilm A, Pitman R, Daniel M D, Chrystie I, McClure M O
Department of Communicable Diseases, Jefferiss Research Trust Laboratories, St Mary's Hospital Medical School, London, United Kingdom.
Virology. 1995 Feb 20;207(1):217-28. doi: 10.1006/viro.1995.1068.
Few foamy (spuma) retroviruses have been investigated in molecular detail, despite their previous isolation from several mamalian species, including ten neutralization serotypes from various primates. Here, we have studied a new gorilla foamy virus (SFV-Gg) and investigated its functional and phylogenetic relationship to the human (HFV) and other primate foamy viruses, including that recently described in orangutans (SFV-11). Nucleotide sequencing of PCR products obtained from the R/U5 region of the LTR, gag, and pol genes revealed a close relationship between HFV and three chimpanzee isolates (SFV-6, SFV-7, and SFV-cpz). The SFV-Gg, SFV-11, rhesus macaque (SFV-1), and African green monkey (SFV-3) isolates were more divergent. To explore functional relationships, primate foamy virus transactivation of HFV LTR driven beta-galactosidase expression in a newly constructed cell line, BHLL, was investigated. HFV, SFV-6, and SFV-7 potently transactivated HFV LTR driven lacZ gene expression, SFV-Gg induced expression approximately 10-fold less efficiently, and SFV types 1, 2, 3, and 11 did not significantly transactivate the HFV LTR. It was, thus, possible to assay serum neutralizing activity in SFV-infected primates against HFV, SFV-6, and SFV-7 by reduction of beta-galactosidase activity following infection of the indicator cell line. Sera from infected chimpanzees and gorillas neutralized, to varying degrees, each of these three viruses, whereas orangutan sera did not. Our results, based on DNA sequences and functional assays, support the conclusion that HFV is closely related to foamy viruses of chimpanzee origin.
尽管之前已从包括来自各种灵长类动物的十种中和血清型在内的几种哺乳动物物种中分离出少数泡沫逆转录病毒，但对其进行的分子细节研究却很少。在此，我们研究了一种新的大猩猩泡沫病毒（SFV-Gg），并调查了它与人类泡沫病毒（HFV）以及其他灵长类泡沫病毒（包括最近在猩猩中描述的SFV-11）的功能和系统发育关系。从长末端重复序列（LTR）的R/U5区域、gag和pol基因获得的PCR产物的核苷酸测序显示，HFV与三种黑猩猩分离株（SFV-6、SFV-7和SFV-cpz）之间存在密切关系。SFV-Gg、SFV-11、恒河猴（SFV-1）和非洲绿猴（SFV-3）分离株的差异更大。为了探索功能关系，我们在新构建的细胞系BHLL中研究了灵长类泡沫病毒对HFV LTR驱动的β-半乳糖苷酶表达的反式激活作用。HFV、SFV-6和SFV-7能有效地反式激活HFV LTR驱动的lacZ基因表达，SFV-Gg诱导表达的效率约低10倍，而1型、2型、3型和11型SFV则不能显著反式激活HFV LTR。因此，通过在指示细胞系感染后降低β-半乳糖苷酶活性，可以测定感染SFV的灵长类动物血清对HFV、SFV-6和SFV-7的中和活性。来自受感染黑猩猩和大猩猩的血清对这三种病毒都有不同程度的中和作用，而猩猩血清则没有。基于DNA序列和功能分析的结果支持了HFV与源自黑猩猩的泡沫病毒密切相关的结论。
