EXTENSIVE SEQUENCE VARIATION OF FELINE IMMUNODEFICIENCY VIRUS ENV GENES IN ISOLATES FROM NATURALLY INFECTED CATS

EXTENSIVE SEQUENCE VARIATION OF FELINE IMMUNODEFICIENCY VIRUS ENV GENES IN ISOLATES FROM NATURALLY INFECTED CATS
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DOI:
10.1007/bf01309743
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发表时间:
1993-01-01
影响因子:
2.7
通讯作者:
ROBINSON, WF
ROBINSON, WF
中科院分区:
医学4区
文献类型:
--
作者:
GREENE, WK;MEERS, J;ROBINSON, WF

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在一项猫免疫缺陷病毒(FIV)体内进化的研究中,通过聚合酶链反应(PCR)对选定的亚基因组区域进行扩增,通过直接测序检测了从一只持续感染的猫中连续分离的病毒。三株分离株,t90, t91和t92,在三年的时间内获得,在gag和pol基因中已知的保守区域没有变化。此外,从另一只实验性感染了t90的猫身上分离出的分离物中,gag和pol没有发生变化。在包膜糖蛋白gp 120 (env)的n端区域检测到变化。这些突变包括点突变,其中一些突变会导致氨基酸取代,预测的氨基酸变化倾向于在可变结构域内聚集。将t90接种到第二只猫身上,导致的突变模式与从第一只猫身上观察到的三个分离株不同。在所有情况下,来自同一只猫的病毒分离株彼此之间的相关性(环境变异程度为0.5-1.5%)远高于来自其他猫的分离株(环境变异程度为10-12%)。FIV的变化率估计为env基因每年每个位点3.4 × 10(-3)个核苷酸替换,gag和pol基因每年每个位点不到10(-4)个核苷酸替换,这与人类免疫缺陷病毒1的发现一致。gp 120区域的核苷酸和氨基酸变化都具有方向性,表明选择压力影响FIV包膜基因序列。
In an investigation of the evolution of feline immunodeficiency virus (FIV) in vivo, sequential isolates from a persistently infected cat were examined by direct sequencing following amplification of selected subgenomic regions by polymerase chain reaction (PCR). Three isolates, T 90, T 91, and T 92, obtained over a three-year period revealed no changes to regions known to be conserved within gag and pol genes. Additionally, no change occurred within gag and pol in an isolate recovered from a second cat which was experimentally infected with T 90. Changes were detected within an N-terminal region of the envelope glycoprotein gp 120 (env). These consisted of point mutations, some of which would result in amino acid substitutions and the predicted amino acid changes tended to cluster within variable domains. Inoculation of T 90 into a second cat resulted in a different pattern of mutations than that observed for the three isolates from the first cat. In all cases, virus isolates derived from the same cat were much more highly related to each other (extent of env variation was 0.5-1.5%) 1.5%) than to isolates from other cats (10-12% env variation). The rate of change of FIV was estimated to be 3.4 x 10(-3) nucleotide substitutions per site per year for the env gene and less than 10(-4) nucleotide substitutions per site per year for the gag and pol genes, values concordant with that found for human immunodeficiency virus 1. Both nucleotide and amino acid changes in the gp 120 region were found to be directional, suggesting that selective pressures influence FIV envelope gene sequences.