CYTOMEGALOVIRUS DETERMINANT OF REPLICATION IN SALIVARY-GLANDS
CYTOMEGALOVIRUS DETERMINANT OF REPLICATION IN SALIVARY-GLANDS
复制标题
DOI：
10.1128/jvi.66.6.3794-3802.1992
复制
发表时间：
1992-06-01
影响因子：
5.4
通讯作者：
MOCARSKI, ES
中科院分区：
文献类型：
--
作者：
MANNING, WC;STODDART, CA;MOCARSKI, ES
发现携带破坏培养细胞中生长基因表达的缺失突变的鼠巨细胞病毒在小鼠中传播不良。该突变导致病毒基因组中与ie 2基因相邻区域的1.5 kb主要和1.8 kb次要β转录物的表达显著降低。核苷酸序列测定表明，323 bp，包括一个预测的多聚腺苷酸化信号，从这个β-基因删除。在培养的细胞中，突变体的空斑形态和生长特征与亲本或拯救的野生型病毒相似。腹腔内接种BALB/c小鼠后，突变体在唾液腺中的生长显著降低10，000倍，而在肝脏和脾脏中的生长没有显著影响。因此，β基因被表示为sgg 1（唾液腺生长基因1）。无论是鼻内感染，也不是直接接种到唾液腺完全克服了在这个器官的生长限制，这表明sgg 1基因编码的组织嗜性的决定因素。为了研究sgg 1突变对病毒通过血液传播的影响，测定了外周血白细胞中的病毒滴度。在sgg 1突变体和拯救的野生型病毒之间没有发现差异。因此，鼠巨细胞病毒sgg 1基因产物似乎参与病毒在唾液腺细胞中的进入或复制。
Murine cytomegalovirus carrying a deletion mutation disrupting the expression of a gene dispensable for growth in cultured cells was found to disseminate poorly in the mouse. The mutation resulted in a dramatic decrease in the expression of a 1.5-kb major and a 1.8-kb minor beta-transcript from a region adjacent to the ie2 gene in the viral genome. Nucleotide sequence determination indicated that 323 bp, including a predicted polyadenylation signal, was deleted from this beta-gene. In cultured cells, the plaque morphology and growth characteristics of the mutant were similar to those of parental or rescued wild-type viruses. Following intraperitoneal inoculation of BALB/c mice, growth of the mutant in the salivary gland was dramatically reduced 10,000-fold, while growth in the liver and spleen was not dramatically affected. The beta-gene was thus denoted sgg1 (salivary gland growth gene 1). Neither intranasal infection nor direct inoculation into the salivary glands completely overcame the restriction of growth in this organ, suggesting that the sgg1 gene encoded a determinant of tissue tropism. To investigate the impact of the sgg1 mutation on virus dissemination via the blood, the virus titer in peripheral blood leukocytes was determined. No difference was found between the sgg1 mutant and rescued wild-type virus. Thus, murine cytomegalovirus sgg1 gene products appear to be involved in entry or replication of virus in salivary gland cells.