McNearney T, Hornickova Z, Kloster B, Birdwell A, Storch G A, Polmar S H, Arens M, Ratner L
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Pediatr Res. 1993 Jan;33(1):36-42. doi: 10.1203/00006450-199301000-00008.
Four neonates who were infected with a single unit of blood from a human immunodeficiency virus-1 (HIV-1)-infected adult (patient 1) were studied. Two of the infected children (patients II and III) developed symptomatic HIV-1 disease and died within the first 3 y of life. One child (patient IV) died at 8 mo of age of clinical problems that may have been HIV-related. In contrast, one child (patient V) has remained asymptomatic for 7.5 y and has exhibited a very gradual decline in CD4+ cell number. A previous study had shown very limited sequence diversity of isolates from patients I, II, and III (McNearney T et al.: Proc Natl Acad Sci USA 87:1917-1921, 1990). The current study examined additional HIV-1 sequences encoding the principal neutralizing V3 loop of the surface envelope protein of isolates from patients I and V. Amplified sequences were obtained using the polymerase chain reaction from a cultured isolate and uncultured peripheral blood leukocytes, and nucleotide sequences were determined for 13 clones from patient I and 19 clones from patient V. Clones derived from the cultured isolate exhibited less predicted amino acid sequence diversity on average (0-5.2%) than did sequences from uncultured leukocytes (0-19.8% differences). All clones were more closely related to those from patients II and III (0-19.8% amino acid differences) than to other North American or European isolates (18.8-27.0% amino acid differences) or African isolates (41.0-48.0% amino acid differences). Substitutions occurred at sites predicted to modulate host cell tropism and proteolytic cleavage of the V3 loop.(ABSTRACT TRUNCATED AT 250 WORDS)
对4名因输入来自一名感染人类免疫缺陷病毒1型(HIV-1)的成人(患者1)的单单位血液而感染的新生儿进行了研究。两名受感染儿童(患者II和III)出现了有症状的HIV-1疾病,并在生命的前3年内死亡。一名儿童(患者IV)在8个月大时死于可能与HIV相关的临床问题。相比之下,一名儿童(患者V)7.5年来一直无症状,其CD4+细胞数量呈非常缓慢的下降。先前的一项研究表明,患者I、II和III分离株的序列多样性非常有限(McNearney T等人:《美国国家科学院院刊》87:1917-1921,1990)。本研究检测了来自患者I和V的分离株表面包膜蛋白主要中和V3环的其他HIV-1序列。使用聚合酶链反应从培养的分离株和未培养的外周血白细胞中获得扩增序列,并确定了来自患者I的13个克隆和来自患者V的19个克隆的核苷酸序列。与来自未培养白细胞的序列(差异为0-19.8%)相比,源自培养分离株的克隆平均预测氨基酸序列多样性更低(0-5.2%)。所有克隆与患者II和III的克隆(氨基酸差异为0-19.8%)的关系比与其他北美或欧洲分离株(氨基酸差异为18.8-27.0%)或非洲分离株(氨基酸差异为41.0-48.0%)更密切。在预测可调节宿主细胞嗜性和V3环蛋白水解切割的位点发生了替换。(摘要截断于250字)