Klein Sabra L, Marson Aimee L, Scott Alan L, Ketner Gary, Glass Gregory E
The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205-2179, USA.
Brain Behav Immun. 2002 Dec;16(6):736-46. doi: 10.1016/s0889-1591(02)00026-0.
Previous studies illustrate that after inoculation with Seoul virus (i.e., the naturally occurring hantavirus found in Norway rats), adult male rats produce higher antibody responses, exhibit higher Th1 responses (i.e., IgG2a, IL-2, and IFN gamma), and shed virus longer than females, but these difference are not altered by manipulation of sex steroids in adulthood. To determine whether sex steroid hormones organize adult responses to hantavirus infection, at 2-4 days of age, male rats were gonadectomized and female rats were injected with testosterone. As adults, animals were inoculated with 10(4)pfu of Seoul virus. Neonatally gonadectomized males (NGM), control females (CF), and neonatal testosterone-treated females (NTF) had lower anti-Seoul virus IgG and IgG2a responses than control males (CM) 20, 30, and 40 days post-inoculation. Neonatal testosterone treatment had no effect on female antibody responses to infection. NGM, CF, and NTF shed virus in saliva and feces for a shorter duration than CM. There was no effect of neonatal hormone manipulation either on the percentage of animals with detectable virus or on the number of virus copies within each target organ. Genetic males, regardless of hormone manipulation, had higher virus replication in lung tissue than did genetic females. Neonatal sex steroids influence the sexual dimorphism in host immune function but do not modify virus replication in target tissues.
先前的研究表明，接种汉城病毒（即褐家鼠体内自然存在的汉坦病毒）后，成年雄性大鼠产生的抗体反应更高，表现出更高的Th1反应（即IgG2a、IL-2和干扰素γ），且病毒排泄时间比雌性大鼠更长，但成年期对性类固醇进行调控并不会改变这些差异。为了确定性类固醇激素是否会影响成年期对汉坦病毒感染的反应，在2至4日龄时，对雄性大鼠进行去势手术，对雌性大鼠注射睾酮。成年后，给动物接种10⁴噬斑形成单位（pfu）的汉城病毒。在接种后20、30和40天，新生期去势的雄性大鼠（NGM）、对照雌性大鼠（CF）和新生期接受睾酮处理的雌性大鼠（NTF）的抗汉城病毒IgG和IgG2a反应低于对照雄性大鼠（CM）。新生期睾酮处理对雌性动物感染后的抗体反应没有影响。NGM、CF和NTF在唾液和粪便中排泄病毒的持续时间比CM短。新生期激素调控对可检测到病毒的动物百分比或每个靶器官内的病毒拷贝数均无影响。无论激素调控如何，基因雄性大鼠肺组织中的病毒复制都比基因雌性大鼠高。新生期性类固醇会影响宿主免疫功能中的性别二态性，但不会改变靶组织中的病毒复制。
