Antibody response to human papillomavirus (HPV) type 11 in children with juvenile-onset recurrent respiratory papillomatosis (RRP).

We previously established, using an ELISA, the presence of specific antibodies directed at human papillomavirus (HPV) type 11 virions in the sera of patients with condylomata acuminata, mostly a disease of young adults that, like recurrent respiratory papillomatosis (RRP), is caused by two closely related HPVs, types 6 and 11. The present study was done to investigate if children with RRP can make viral-specific antibodies to an infection that is acquired at birth. Using the same ELISA, we studied the sera of 32 children with biopsy-documented juvenile-onset RRP and compared them to the sera of 31 control children. The median (and interquartile range) of the OD values in the controls and the cases was 0.078 (0.003, 0.101) and 0.230 (0.063, 0.725), respectively, a statistically significant difference (P = 0.001). Among the cases, there was no difference in seroreactivity between children with HPV-11-induced RRP and those with HPV-6-induced RRP (P = 0.31). Since HPV-11 viral particles do bind to the ELISA plate and remain intact and accessible to antibodies, we conclude that children with RRP, like adults with condylomata acuminata, develop antibodies directed at HPV-11 virions.     

荧光定量聚合酶链反应检测人乳头瘤病毒6/11型

目的 了解女性阴道炎患者人乳头瘤病毒6／11型（HPV6／11）的感染情况。方法 用荧光定量聚合酶链反应（FQ－PCR）技术检测129例门诊患者阴道分泌物中HPV6／11的病毒拷贝数。结果 共检出HPV6／11阳笥者47例,阳性率为36．43％;拷贝数在10^5以上者39例,占阳性者中的82．98％;40岁以上年龄组阳性率高且病毒复制量均在10^5以上。结论 中老年阴道炎患者就诊晚,感染重。FQ－PCR检测HPV敏感、快速、准确,特别是其定量特点对临床很有意义。     

Transmission of human papillomavirus type 11 infection by desquamated cornified cells

While much is known about the human papillomavirus (HPV) productive cycle, the mechanisms of virion transmission from person to person are poorly understood. The keratinocyte is the target cell of HPV infection. As keratinocytes differentiate, nuclei are lost and the cornified cell envelope develops. Layers of these desquamated cornified cells (DCCs) are continuously shed from the stratum corneum. Release of HPV requires the cornified cell envelope, a normally very durable structure, to break apart, liberating the contents of the cell. In differentiated keratinocytes infected with HPV 11, the cornified cell envelope is abnormally thin and fragile. In this study, DCCs from HPV 11-infected genital epithelium were used to investigate the mechanisms of viral transmission. First, HPV 11-infected tissue was examined for the presence of virions by transmission electron microscopy. Virions were observed in the nuclei of differentiated keratinocytes. In addition, virions were detected in the cytoplasm of DCCs that had undergone nuclear dissolution. Rarely, virions were observed outside of cells. Next, infectivity of intact and ruptured DCCs was tested in an assay performed in the athymic mouse xenograft system. High-titer cesium chloride gradient-purified HPV 11 virions infected 100% of recovered xenografts. Using intact DCCs derived from HPV 11-infected tissue, 62.5% of recovered xenografts were infected. To test the effects of mechanical stress on infectivity, DCCs were ruptured by sonication and used in the infectivity assay. The infectivity rate increased to 90%. We conclude that DCCs serve as vehicles for efficient, concentrated delivery of virions in HPV 11 infection.     

A unique verrucous anogenital tumor associated with type 6b-related human papillomavirus

Multiple dark brown papillomatous tumors, showing some histological features of verrucous carcinoma or giant condyloma, developed mainly in the anogenital region of a Japanese woman. The tumors first appeared when she was 51 years old and annoyed her for over 20 years with several recurrences without any frank malignant transformation, after surgery. Immunohistochemically, papillomavirus genus-specific antigen was demonstrated only in small foci of the lesions resected at first operation. Southern blot analysis revealed human papillomavirus type 6b-related DNA in a surgically resected specimen. The possible role of the human papillomavirus in the genesis of this unique tumor is discussed.     

DNA dot-blot hybridization implicates human papillomavirus type 11-DNA in epithelioma cuniculatum

Epithelioma cuniculatum is a rare, low-grade squamous cell carcinoma, belonging to the group of verrucous carcinomas. Evidence is presented that suggests that human papilloma virus type-11 may be involved in the pathogenesis of epithelioma cuniculatum. HPV-DNA was detected by dot-blot hybridization with 32P-labelled probe DNA. Plasmids containing HPV-DNA were isolated by the benzoylated naphthoylated DEAE cellulose method (BND-method), an improved procedure for routine detection of HPV-DNA.     

Structural analysis of human papillomavirus type 6c isolates from condyloma acuminatum and juvenile-onset and adult-onset laryngeal papillomata

The human papillomavirus type 6c (HPV-6c) genome was molecularly cloned from biopsy specimens of a juvenile-onset and an adult-onset respiratory-tract papillomata and a condyloma acuminatum of the cervix. To determine if the genital-tract isolate and respiratory-tract isolates contain divergent sequences that may account for a difference in tissue trophism or for a difference in the age of onset of the disease, fine-structure mapping, heteroduplex analysis by electron microscopy, and nucleotide sequencing were used to examine the sequence relationship among these HPV-6c isolates. No differences were found in the digestion among these HPV-6c isolates. No differences were found in the digestion patterns with 23 restriction enzymes. Heteroduplex analysis among the three genomes demonstrated that they were colinear without apparent deletions or rearrangements and had greater than 90% sequence identity. In heteroduplex analyses with a different subtype (HPV-6e) that was molecularly cloned from a genital wart, the genomes were colinear with greater than 90% sequence identity over 90% of their length. The most divergent region had 75–80% sequence identity and was localized to the part of the genome containing the E5a and E5b open reading frames (ORFs). Comparison of the sequence of 1430 nucleotides in this region for two of the HPV-6c isolates did not identify any differences between them. Comparison with the published sequences of HPV-6b identified deletions/insertions and base changes with approximately 75% sequence identity, and comparison with HPV-11 identified only six base changes. Conservation of sequences in the E4-E5 region and similarity in the restriction enzyme maps demonstrated that HPV-6c and HPV-11 are independent isolates of the same HPV-6 subtype.     

Genomic characterization of a novel bovine papillomavirus type 28

Virus Genes - Infection of bovine papillomavirus (BPV) has been associated with mucosal and/or cutaneous tumor development in bovids. To date, up to 27 genotypes of BPVs have been identified and...     

Squamous carcinoma arising in a giant peri-anal condyloma associated with human papillomavirus types 6 and 11

A case is reported of squamous carcinoma of the peri-anal region arising in a giant condyloma. In situ DNA hybridization showed human papillomavirus (HPV) types 6 and 11. These HPV types are commonly demonstrated in ano-genital condylomas but have not previously been reported in association with malignant change at this site.     

人乳头瘤病毒11型L1/E7嵌合DNA疫苗的构建及其诱导的免疫效应

Objective To construct chimerical DNA vaccine plasmid of human papiUomavirus type 11 (HPV11) L1-E7, and to evaluate its immunogenicity. Methods Molecular cloning techniques were used to construct recombinant plasmid PeDNA3 L1-E7 as a DNA vaccine. BALB/c mice were vaccinated with DNA recombinants through muscle injection. IL-2 and γ-INF secreted by immunized spleens lymphocyte and HPV 11 LI or E7 specific antibodies were assayed by ELISA method. Spleens lymphocyte proliferation was measured by MTT assay. Results The chimerical DNA plasmid of pcDNA3 LI-E7 was constructed correctly. Specific anti-HPV11 E7 and L1 antibodies, specific lymphocyte proliferation and secretions of IL-2 and γ-INF were detected in vaccinated mice. Conclusion Specific immune response, including cellular immunity and humoral immunity, could been detected in mice vaccinated with chimerical DNA vaccine of pcDNA3 L1-E7.     

人乳头瘤病毒11型L1/E7嵌合DNA疫苗的构建及其诱导的免疫效应

Objective To construct chimerical DNA vaccine plasmid of human papiUomavirus type 11 (HPV11) L1-E7, and to evaluate its immunogenicity. Methods Molecular cloning techniques were used to construct recombinant plasmid PeDNA3 L1-E7 as a DNA vaccine. BALB/c mice were vaccinated with DNA recombinants through muscle injection. IL-2 and γ-INF secreted by immunized spleens lymphocyte and HPV 11 LI or E7 specific antibodies were assayed by ELISA method. Spleens lymphocyte proliferation was measured by MTT assay. Results The chimerical DNA plasmid of pcDNA3 LI-E7 was constructed correctly. Specific anti-HPV11 E7 and L1 antibodies, specific lymphocyte proliferation and secretions of IL-2 and γ-INF were detected in vaccinated mice. Conclusion Specific immune response, including cellular immunity and humoral immunity, could been detected in mice vaccinated with chimerical DNA vaccine of pcDNA3 L1-E7.     

人乳头瘤病毒11型L1/E7嵌合DNA疫苗的构建及其诱导的免疫效应

Objective To construct chimerical DNA vaccine plasmid of human papiUomavirus type 11 (HPV11) L1-E7, and to evaluate its immunogenicity. Methods Molecular cloning techniques were used to construct recombinant plasmid PeDNA3 L1-E7 as a DNA vaccine. BALB/c mice were vaccinated with DNA recombinants through muscle injection. IL-2 and γ-INF secreted by immunized spleens lymphocyte and HPV 11 LI or E7 specific antibodies were assayed by ELISA method. Spleens lymphocyte proliferation was measured by MTT assay. Results The chimerical DNA plasmid of pcDNA3 LI-E7 was constructed correctly. Specific anti-HPV11 E7 and L1 antibodies, specific lymphocyte proliferation and secretions of IL-2 and γ-INF were detected in vaccinated mice. Conclusion Specific immune response, including cellular immunity and humoral immunity, could been detected in mice vaccinated with chimerical DNA vaccine of pcDNA3 L1-E7.     

人乳头瘤病毒11型L1/E7嵌合DNA疫苗的构建及其诱导的免疫效应

Objective To construct chimerical DNA vaccine plasmid of human papiUomavirus type 11 (HPV11) L1-E7, and to evaluate its immunogenicity. Methods Molecular cloning techniques were used to construct recombinant plasmid PeDNA3 L1-E7 as a DNA vaccine. BALB/c mice were vaccinated with DNA recombinants through muscle injection. IL-2 and γ-INF secreted by immunized spleens lymphocyte and HPV 11 LI or E7 specific antibodies were assayed by ELISA method. Spleens lymphocyte proliferation was measured by MTT assay. Results The chimerical DNA plasmid of pcDNA3 LI-E7 was constructed correctly. Specific anti-HPV11 E7 and L1 antibodies, specific lymphocyte proliferation and secretions of IL-2 and γ-INF were detected in vaccinated mice. Conclusion Specific immune response, including cellular immunity and humoral immunity, could been detected in mice vaccinated with chimerical DNA vaccine of pcDNA3 L1-E7.     

人乳头瘤病毒11型L1/E7嵌合DNA疫苗的构建及其诱导的免疫效应

目的 构建人乳头瘤病毒11型L1/E7嵌合DNA疫苗pcDNA3 L1-E7并研究其在小鼠中诱导的免疫效应.方法 用分子克隆技术构建重组真核表达质粒peDNA3 L1-E7.重组质粒DNA股四头肌注射免疫小鼠,用ELISA方法 检测L1、E7特异性抗体和脾细胞分泌的IL-2、γ-INF;MTT法检测脾淋巴细胞增殖反应.结果 成功构建pcDNA3 L1-E7.免疫小鼠后,重组质粒可诱导机体产生特异性脾淋巴细胞增殖及IL-2、γ-INF分泌增加,并诱导机体产生HPV 11-E7 IgG和HPV 11-L1 IgG抗体.结论 嵌合DNA疫苗pcDNA3 L1-E7能诱导小鼠产生特异性的细胞免疫和体液免疫反应.     

人乳头瘤病毒11型L1/E7嵌合DNA疫苗的构建及其诱导的免疫效应

Objective To construct chimerical DNA vaccine plasmid of human papiUomavirus type 11 (HPV11) L1-E7, and to evaluate its immunogenicity. Methods Molecular cloning techniques were used to construct recombinant plasmid PeDNA3 L1-E7 as a DNA vaccine. BALB/c mice were vaccinated with DNA recombinants through muscle injection. IL-2 and γ-INF secreted by immunized spleens lymphocyte and HPV 11 LI or E7 specific antibodies were assayed by ELISA method. Spleens lymphocyte proliferation was measured by MTT assay. Results The chimerical DNA plasmid of pcDNA3 LI-E7 was constructed correctly. Specific anti-HPV11 E7 and L1 antibodies, specific lymphocyte proliferation and secretions of IL-2 and γ-INF were detected in vaccinated mice. Conclusion Specific immune response, including cellular immunity and humoral immunity, could been detected in mice vaccinated with chimerical DNA vaccine of pcDNA3 L1-E7.     

人乳头瘤病毒11型L1/E7嵌合DNA疫苗的构建及其诱导的免疫效应

Objective To construct chimerical DNA vaccine plasmid of human papiUomavirus type 11 (HPV11) L1-E7, and to evaluate its immunogenicity. Methods Molecular cloning techniques were used to construct recombinant plasmid PeDNA3 L1-E7 as a DNA vaccine. BALB/c mice were vaccinated with DNA recombinants through muscle injection. IL-2 and γ-INF secreted by immunized spleens lymphocyte and HPV 11 LI or E7 specific antibodies were assayed by ELISA method. Spleens lymphocyte proliferation was measured by MTT assay. Results The chimerical DNA plasmid of pcDNA3 LI-E7 was constructed correctly. Specific anti-HPV11 E7 and L1 antibodies, specific lymphocyte proliferation and secretions of IL-2 and γ-INF were detected in vaccinated mice. Conclusion Specific immune response, including cellular immunity and humoral immunity, could been detected in mice vaccinated with chimerical DNA vaccine of pcDNA3 L1-E7.