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Squamous cell papilloma (SCP) in the upper aero-digestive tract is a rare disease entity with bimodal age presentation both at childhood and in adults. It originates from stratified squamous and/or respiratory epithelium. Traditionally, SCPs have been linked to chemical or mechanical irritation but, since the 1980s, they have also been associated with human papillomavirus (HPV) infection. Approximately 30% of the head and neck SCPs are associated with HPV infection, with this association being highest for laryngeal papillomas (76-94%), followed by oral (27-48%), sinonasal (25-40%), and oropharyngeal papillomas (6-7%). There is, however, a wide variation in HPV prevalence, the highest being in esophageal SCPs (11-57%). HPV6 and HPV11 are the two main HPV genotypes present, but these are also high-risk HPVs as they are infrequently detected. Some 20% of the oral and oropharyngeal papillomas also contain cutaneous HPV genotypes. Despite their benign morphology, some SCPs tend to recur and even undergo malignant transformation. The highest malignant potential is associated with sinonasal inverted papillomas (7-11%). This review discusses the evidence regarding HPV etiology of benign SCPs in the upper aero-digestive tract and their HPV-related malignant transformation. In addition, studies on HPV exposure at an early age are discussed, as are the animal models shedding light on HPV transmission, viral latency, and its reactivation.

Human herpesviruses 6A and 6B (HHV-6A and HHV-6B) are human viruses capable of chromosomal integration. Approximately 1% of the human population carries one copy of HHV-6A/B integrated into every cell in their body, referred to as inherited chromosomally integrated human herpesvirus 6A/B (iciHHV-6A/B). Whether iciHHV-6A/B is transcriptionally active in vivo and how it shapes the immunological response are still unclear. In this study, we screened DNA sequencing (DNA-seq) and transcriptome sequencing (RNA-seq) data for 650 individuals available through the Genotype-Tissue Expression (GTEx) project and identified 2 iciHHV-6A- and 4 iciHHV-6B-positive candidates. When corresponding tissue-specific gene expression signatures were analyzed, low levels HHV-6A/B gene expression was found across multiple tissues, with the highest levels of gene expression in the brain (specifically for HHV-6A), testis, esophagus, and adrenal gland. U90 and U100 were the most highly expressed HHV-6 genes in both iciHHV-6A- and iciHHV-6B-positive individuals. To assess whether tissue-specific gene expression from iciHHV-6A/B influences the immune response, a cohort of 15,498 subjects was screened and 85 iciHHV-6A/B + subjects were identified. Plasma samples from iciHHV-6A/B + and age- and sex-matched controls were analyzed for antibodies to control antigens (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and influenza virus [FLU]) or HHV-6A/B antigens. Our results indicate that iciHHV-6A/B + subjects have significantly more antibodies against the U90 gene product (IE1) than do non-iciHHV-6-positive individuals. Antibody responses against EBV and FLU antigens or HHV-6A/B gene products either not expressed or expressed at low levels, such as U47, U57, and U72, were identical between controls and iciHHV-6A/B + subjects. CMV-seropositive individuals with iciHHV-6A/B + have more antibodies against CMV pp150 than do CMV-seropositive controls. These results argue that spontaneous gene expression from integrated HHV-6A/B leads to an increase in antigenic burden that translates into a more robust HHV-6A/B-specific antibody response. IMPORTANCE HHV-6A and -6B are human herpesviruses that have the unique property of being able to integrate into the telomeric regions of human chromosomes. Approximately 1% of the world's population carries integrated HHV-6A/B genome in every cell of their body. Whether viral genes are transcriptionally active in these individuals is unclear. By taking advantage of a unique tissue-specific gene expression data set, we showed that the majority of tissues from iciHHV-6 individuals do not show HHV-6 gene expression. Brain and testes showed the highest tissue-specific expression of HHV-6 genes in two separate data sets. Two HHV-6 genes, U90 (immediate early 1 protein) and U100 (glycoproteins Q1 and Q2), were found to be selectively and consistently expressed across several human tissues. Expression of U90 translates into an increase in antigen-specific antibody response in iciHHV-6A/B + subjects relative to controls. Future studies will be needed to determine the mechanism of gene expression, the effects of these genes on human gene transcription networks, and the pathophysiological impact of having increased viral protein expression in tissue in conjunction with increased antigen-specific antibody production., (Copyright © 2019 Peddu et al.)

Human papillomavirus (HPV) infection is one of the hypothesized causes of esophageal squamous cell carcinoma (ESCC), but the etiological association remains uncertain. It was postulated that other infectious agents together with HPV may increase the risk of ESCC. The current investigation aimed to explore the presence of a new human tumor virus, Merkel cell polyomavirus (MCPyV), together with HPV in ESCC tumors and non-cancerous esophageal samples in northern Iran. In total, 96 esophageal samples (51 with ESCC, and 45 without esophageal malignancy) were examined. HPV DNA was detected in esophageal specimens of 16 out of the 51 ESCC cases (31.4 %) and 20 out of the 45 non-cancerous samples (44.4 %). Untypable HPV genotypes were recognized in high rates in cancerous (75.0 %) and non-cancerous (55.0 %) esophageal specimens. MCPyV DNA was detected in esophageal specimens of 23 out of the 51 ESCC cases (45.1 %) and 16 out of the 45 non-cancerous samples (35.6 %). The mean MCPyV DNA copy number was 1.0 × 10(-5) ± 2.4 × 10(-5) and 6.0 × 10(-6) ± 1.3 × 10(-5) per cell in ESCC cases and non-cancerous samples, respectively. There was no statistically significant difference between cancerous and non-cancerous samples regarding mean MCPyV DNA load (P = 0.353). A bayesian logistic regression model adjusted to the location of esophageal specimen and MCPyV infection, revealed a significant association between HPV and odds of ESCC (OR, 2.45; 95 % CI: 1.01-6.16). This study provides the evidence of the detection of the MCPyV DNA at a low viral copy number in cancerous and non- cancerous esophageal samples.

A specific real time reverse transcription polymerase chain reaction (RT-PCRrt) for the detection of foot-and-mouth disease virus was validated using the LightCycler thermocycler 2.0 and its reagents as recommended by the World Organization for Animal Health and was assessed for the detection of the virus in acute infection of cattle experimentally vaccinated and challenged with virus A Argentina/2001 or A24 Cruzeiro. The technique proved to be robust, showing coefficients of variation lower than 4% for different ARN extractions, days or repetitions and was able to detect up to 0,4 TCID 50%, and/or up to 100 RNA molecules. In probang samples, diagnostic sensitivity was 93.1 (95% CI 86.5-96.6) and diagnostic specificity 100 (95% CI 96.3-100). The results of the challenge in vaccinated or multivaccinated bovines showed that although there were high levels of clinical protection in the vaccinated group, FMDV could be detected in all challenged groups. However, detection was 100 times lower in immunized animals., (Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España. All rights reserved.)

A novel avipoxvirus caused diphtheritic lesions in the oesophagus of five and in the bronchioli of four Magellanic penguins (Spheniscus magellanicus) and also cutaneous lesions in eight Magellanic penguins housed in outdoor enclosures in a Rehabilitation Centre at Florianópolis, Santa Catarina State, Brazil. At the same time, another avipoxvirus strain caused cutaneous lesions in three Magellanic penguins at a geographically distinct Rehabilitation Centre localized at Vila Velha, Espírito Santo State, Brazil. Diagnosis was based on clinical signs, histopathology and use of the polymerase chain reaction (PCR). Clinical signs in the penguins included cutaneous papules and nodules around eyelids and beaks, depression and restriction in weight gain. The most common gross lesions were severely congested and haemorrhagic lungs, splenomegaly and cardiomegaly. Histological examination revealed Bollinger inclusion bodies in cutaneous lesions, mild to severe bronchopneumonia, moderate periportal lymphocytic hepatitis, splenic lymphopenia and lymphocytolysis. Other frequent findings included necrotizing splenitis, enteritis, oesophagitis, dermatitis and airsacculitis. Cytoplasmic inclusion bodies were seen within oesophageal epithelial cells in five birds and in epithelial cells of the bronchioli in four penguins. DNA from all samples was amplified from skin tissue by PCR using P4b-targeting primers already described in the literature for avipoxvirus. The sequences showed two different virus strains belonging to the genus Avipoxvirus of the Chordopoxvirinae subfamily, one being divergent from the penguinpox and avipoxviruses already described in Magellanic penguins in Patagonia, but segregating within a clade of canarypox-like viruses implicated in diphtheritic and respiratory disease.

Studies have shown immunological and morphological alterations in the esophagus during the course of AIDS. Esophageal postmortem samples of 22 men with AIDS autopsied in a teaching hospital between 1982 and 2009 were collected. We carried out revision of the autopsy reports and medical records, morphometric analysis (Image J and KS-300 Kontron-Zeiss), and immunohistochemical (anti-S100, anti-IgA, anti-IgG, and anti-IgM) analysis of the esophagus. In accordance with most of the parameters evaluated, age and the smoking habit harmed the esophageal local immunity, whereas the use of antiretroviral therapy improved the immune characteristics of this organ. Patients with esophagitis also presented immunological fragility of the esophagus. This leads to the conclusion that alterations in the esophageal epithelium of patients with AIDS are not only caused by direct action of HIV but also the clinical and behavioral characteristics of the patient.

Background: Evaluation of Human papilloma virus (HPV) and its association with promoter methylation of candidate genes, p53 and Aurora A in esophageal cancer., Materials and Methods: One hundred forty-one esophageal tissue samples from different pathologies were evaluated for HPV infection by PCR, while the promoter methylation status of p53 and Aurora A was assessed by methylation-specific restriction based PCR assay. Statistical analyses were performed with MedCalc and MDR software., Results: Based on endoscopy and histopathology, samples were categorized: cancers (n=56), precancers (n=7), esophagitis (n=19) and normals (n=59). HPV infection was found to be less common in cancers (19.6%), whereas its prevalence was relatively high in precancers (71.4%), esophagitis (57.8%) and normals (45.7%). p53 promoter methylation did not show any significant difference between cancer and normal tissues, whereas Aurora A promoter methylation demonstrated significant association with disease (p=0.00016, OR:5.6452, 95%CI:2.18 to 14.6) when compared to normals. Aurora A methylation and HPV infection was found in a higher percentages of precancer (66.6%), esophagitis (54.5%) and normal (45.2%) when compared to cancers (14.2%)., Conclusions: Aurora A promoter methylation is significantly associated with esophageal cancer, but the effect of HPV infection on this epigenetic alteration is not significant. However MDR analysis showed that the hypostatic effect of HPV was nullified when the cases had Aurora methylation and tobacco exposure. Further HPV sub-typing may give an insight into its reduced prevalence in esophageal cancer verses normal tissue. However, with the present data it is difficult to assign any significant role to HPV in the etiopathology of esophageal cancer.

Currently, over 15% of new HIV infections occur in children. Breastfeeding is a major contributor to HIV infections in infants. This represents a major paradox in the field because in vitro, breast milk has been shown to have a strong inhibitory effect on HIV infectivity. However, this inhibitory effect has never been demonstrated in vivo. Here, we address this important paradox using the first humanized mouse model of oral HIV transmission. We established that reconstitution of the oral cavity and upper gastrointestinal (GI) tract of humanized bone marrow/liver/thymus (BLT) mice with human leukocytes, including the human cell types important for mucosal HIV transmission (i.e. dendritic cells, macrophages and CD4⁺ T cells), renders them susceptible to oral transmission of cell-free and cell-associated HIV. Oral transmission of HIV resulted in systemic infection of lymphoid and non-lymphoid tissues that is characterized by the presence of HIV RNA in plasma and a gradual decline of CD4⁺ T cells in peripheral blood. Consistent with infection of the oral cavity, we observed virus shedding into saliva. We then evaluated the role of human breast milk on oral HIV transmission. Our in vivo results demonstrate that breast milk has a strong inhibitory effect on oral transmission of both cell-free and cell-associated HIV. Finally, we evaluated the effect of antiretrovirals on oral transmission of HIV. Our results show that systemic antiretrovirals administered prior to exposure can efficiently prevent oral HIV transmission in BLT mice.

Background: Foot-and mouth disease (FMD) is an acute, febrile, and contagious vesicular disease affecting cloven-hoofed animals. Some animals may become persistent infected carriers when they contact FMD virus (FMDV), and persistent infected animals are a dangerous factor to cause FMD outbreak., Findings: 300 OP (oesophageal-pharyngeal) fluid samples were collected from cattle without clinic symptom after one month FMD circulated in 2010 in China. A FMDV strain was isolated when a positive OP sample was passed in BHK21 cell line. The strain, named O/CHN/2010/33-OP, was detected to be O/Myanmar/1998 lineage with VP1 DNA sequence comparison. In order to testify its infectivity, two cattle were challenged with OP fluid and three pigs were put into the same pen for direct contact infection. The result showed that one of the cattle and one of the pigs appeared FMD clinic symptoms respectively. Furthermore, two cattle (three pigs were also put into the same pen for direct contact infection) and three pigs were inoculated with O/CHN/2010/33-OP cell passaged strain. The result showed that one of the challenged pigs appeared FMD clinic symptoms. Two cattle and three pigs in the same pen did not appeared FMD clinic symptoms, but the sera antibody and their OP fluid of two cattle were positive. Meanwhile, the spinal cords of three pigs in the same pen with two cattle were positive detected with multiplex- RT-PCR., Conclusion: The persistent infection strain O/CHN/2010/33-OP has infectivity and pathogenicity to cattle and pigs, and infected cattle may transmit the virus to pigs although its virulence was lower than the circulated strain O/CHN/Mya98/2010.

Reports of combined candidal and herpetic esophagitis in immunocompetent states are rare and sporadic. A 44-year-old previously healthy lady presented with a one week history of progressive dysphagia, odynophagia and fever. Esophagogastroduodenoscopy (EGD) showed extensive desquamation of the entire esophagus except for distal 4 cm. Histopathological examination revealed ulcerated and inflamed squamous epithelium with the margin of ulcer showing a few overhanging squamous cells with dense eosinophilic cytoplasm, multinucleated and faceted nuclei with glassy chromatin, and an occasional Cowdry type A intranuclear inclusion bodies. Few candidal spores were seen in the underlying stroma. Intravenous acyclovir, fluconazole and pantoprazole were initiated. Oral analgesics were given for pain relief. She was treated for a total of 14 days. She showed significant improvement and was tolerating oral intake after discharge. The patient was asymptomatic with no evidence of recurrence at a 2-month follow-up.

Background: The gut-associated lymphoid tissue (GALT) is the largest lymphoid organ infected by human immunodeficiency virus type 1 (HIV-1). It serves as a viral reservoir and host-pathogen interface in infection. This study examined whether different parts of the gut and peripheral blood lymphocytes (PBL) contain different drug-resistant HIV-1 variants., Methods: Gut biopsies (esophagus, stomach, duodenum and colon) and PBL were obtained from 8 HIV-1 infected preHAART (highly active antiretroviral therapy) patients at three visits over 18 months. Patients received AZT, ddI or combinations of AZT/ddI. HIV-1 Reverse transcriptase (RT)-coding sequences were amplified from viral DNA obtained from gut tissues and PBL, using nested PCR. The PCR fragments were cloned and sequenced. The resulting sequences were subjected to phylogenetic analyses, and antiretroviral drug mutations were identified., Results: Phylogenetic and drug mutation analyses revealed differential distribution of drug resistant mutations in the gut within patients. The level of drug-resistance conferred by the RT sequences was significantly different between different gut tissues and PBL, and varied with antiretroviral therapy. The sequences conferring the highest level of drug-resistance to AZT were found in the colon., Conclusion: This study confirms that different drug-resistant HIV-1 variants are present in different gut tissues, and it is the first report to document that particular gut tissues may select for drug resistant HIV-1 variants.

A case of severe human cytomegalovirus esophagitis after short-term corticosteroid therapy in a patient with no other apparent cause of immunodeficiency, such as human immunodeficiency virus infection, neoplasia, or previous organ transplantation, is described herein. The cytomegalovirus esophagus infection was successfully treated with ganciclovir.

Herpes simplex esophagitis (HSE) is well documented in immunosuppressed patients. However, it is rare in the immunocompetent host. We present a case of HSE in a 21 year-old healthy lady who was admitted to our unit with dysphagia, odynophagia and chest pain. Clinical examination revealed mild epigastric tenderness and admission bloods including full blood picture, electrolytes and inflammatory markers were normal. She underwent an esophagogastroduodenoscopy (EGD) which revealed severe exudative, well-circumscribed ulcerations in her distal esophagus. Biopsies confirmed severe esophagitis with acute ulceration and subsequent polymerase chain reaction (PCR) confirmed herpes simplex virus (HSV) type 1. Subsequent assessment failed to identify an immune disorder. HSE should be suspected when faced with characteristic endoscopic findings, even if the patient is immunocompetent. When the diagnosis of HSE is confirmed, an immune deficiency should be sought.

Aim: To look for the evidence of human papilloma virus (HPV) infection in esophageal squamous cell carcinomas (ESCC) and to investigate the potential role and epidemiology of HPV infection in the pathogenesis of esophageal carcinomas in Henan emigrants., Methods: Papilloma virus(PV) and HPV were determined by Ultrasensive S-P immunohistochemistry (IHC) and in situ hybridization (ISH)in esophageal carcinoma tissues (82 cases) and the normal mucosa (40 cases)., Results: IHC revealed that the positive rate of PV was 75.0%, 68.18% and 72.5% respectively while the HPV (16/18-E6) positive rate was 45.0%,36.36%, 37.5%, respectively in esophageal carcinoma tissue specimens from Henan emigrants,the local citizens and patients in Hubei Cancer Hospital. The PV and HPV (16/18-E6) were negative in all normal esophageal mucosa specimens. No correlation was found between HPV in esophageal squamous cell carcinoma tissues and in grade 1-3 esophageal squamous cell carcinoma cells. In situ hybridization showed that the HPV (16/18) DNA positive rate was 30.0%, 31.8%, 25.0%, respectively in the 3 groups of samples. No positive hybridization signal was found in 40 normal esophageal mucosa specimens. The positive rate of HPV (16/18) DNA in the esophageal carcinoma specimens was significantly higher than that in normal mucosa specimens (P<0.05). The positive rate was not different among the 3 groups of esophageal carcinoma tissue specimens (P>0.05)., Conclusion: HPV infection is high in esophageal carcinoma of Henan emigrants, local residents and patients in Hubei Cancer Hospital.HPV is closely related with esophageal squamous cell carcinoma. HPV infection may play an important role in esophageal squamous cell carcinoma.

To investigate whether foot-and-mouth disease virus (FMDV) RNA loads in oesophageal-pharyngeal fluid (OP-fluid) in the early course of infection is related to the outcome of virus persistence, viral RNA in OP-fluid samples from cattle experimentally infected with FMDV type O was quantitatively analysed by using a quantitative real-time RT-PCR. Viral RNA was detected within 24 h post-infection (p.i.) in all infected animals. Rapid virus replication led to peak levels of viral RNA load by 30-53 h p.i., and then the load declined at various rates. In some animals (n=12, so-called non-carriers) viral RNA became undetectable between 7 and 18 days p.i. In contrast, in persistently infected animals (n=12, so-called carriers) viral RNA persisted in OP-fluid samples at detectable levels beyond 28 days p.i. Analysis of early viral decay/clearance and virus clearance half-life in OP-fluid samples showed that the extent of reduction of viral RNA in OP-fluid samples immediately following peak levels is a critical determinant of the outcome of FMDV persistence.

Aim: To investigate the putative role of human papillomavirus (HPV) infection in the carcinogenesis of esophageal squamous cell carcinoma in China., Methods: Twenty-three esophageal squamous cell carcinoma samples and the distal normal epithelium from Shanxi Province, and 25 more esophageal squamous cell carcinoma samples from Anyang city, two areas with a high incidence of esophageal cancer in China, were detected for the existence of HPV-16 DNA by PCR, mRNA in situ hybridization (ISH) and immunohistochemistry (IHC) targeting HPV-16 E6 gene., Results: There were approximately 64 % (31/48) patients having HPV-16 DNA in tumor samples, among them nearly two-thirds (19/31) samples were detected with mRNA expression of HPV-16 E6. However, in the normal esophageal epithelium from cancer patients, the DNA and mRNA of HPV-16 were found with much less rate: 34.7 % (8/23) and 26.1 % (6/23) respectively. In addition, at protein level detected by IHC assay, 27.1 % (13/48) tumor samples had virus oncoprotein E6 expression, while only one case of normal epithelium was found positive., Conclusion: HPV infection, especially type 16, should be considered as a risk factor for esophageal malignancies in China.

We studied cytogenesis, telomere and telomerase, and c-myc, ras, bcl-2, and p53 genes of cells in the progressive process of immortal epithelial cells from embryonic esophagus induced by human papillomavirus (HPV). The SHEE cell line, established by us, consist of immortalized epithelial cells from the embryonic esophagus induced by genes E6E7 of HPV type 18. It was in initial malignant transformation when cultivated over 60 passages without co-carcinogens. Cells of the 10th, 31st, and 60th passages were represented in the progressive process within the immortal period. In these three stages of the cell line, the modal number of chromosome and karyotypes were analyzed. The telomere length was assayed by Southern blot methods, and the telomerase activity was analyzed by hTR and hTERT assay. C-myc, p53, bcl-2, ras genes were assayed by the multi-PCR method. The morphology of the 10th passage cells exhibited good differentiation, the 60th passage cells were relatively poorly differentiated, and the 31st passage cells differentiated in two distinct ways. The growth characteristics of the 31st and 60th passage cells were weakened at contact-inhibition and anchorage-dependent growth. Karyotypes of three cell passages belonged to hyperdiploid and hypotriploid with abnormal chromosomes +1, +3, +7, +9, +17, +18; del(1)(p32); der(4), t(4;?)(q31;?); der(5),t(5;?)(q31;?); der(13),t(13;13)(p11;q11) and others. Bimodal distribution of chromosomes with more aberrant chromosomes appeared in the 31st and 60th passage cells. Telomere length sharply shortened from normal fetal esophagus to the 10th and 31st passage step by step, but was stable from the 31st to the 60th passage and the telomerase activities measured were expressed at late two passages. p53 mutant was positive in three passages, c-myc was positive in the 31st and the 60th passage K-ras only in the last. The results reveal that changes of chromosomes, telomere length, telomerase activity and certain gene expressions are important events of HPV-immortalized esophageal epithelium cells. All of these changes occurred in dynamic progressive process. This cell line may be useful for the elucidation of the genetic mechanism of cellular immortalization.

Congenital varicella syndrome is a rare complication of varicella-zoster virus (VZV) infection during pregnancy. An infant was exposed to VZV at 18.5 weeks of gestation and had eye and skin abnormalities at birth and persistent feeding difficulties, prompting esophageal biopsies at 12 days and 20 and 20.5 months of age. Esophageal tissues demonstrated specialized intestinal metaplasia (Barrett's esophagus). VZV DNA (in situ hybridization) and proteins (immunohistochemistry and polymerase chain reaction) were found in esophageal epithelial cells adjacent to the Barrett's lesion. Immediate-early 63 protein (IE63) of VZV was demonstrated in the day 12 specimen, and IE62 and the late VZV glycoprotein E (gE) were found in the 20-month specimen. Clinical and endoscopic improvement followed fundoplication and acyclovir therapy, but VZV DNA and IE62 persisted in esophageal tissue. These findings associate VZV with specialized intestinal metaplasia within the esophagus and suggest a novel site for either latent or active VZV infection.

To clarify the role of high risk human papillomavirus (HPV 16, 18 and 33) and Epstein-Barr virus (EBV) infection in esophageal carcinogenesis in relation to expression of mutated p53 antioncogene, we used PCR to amplify DNA sequences of these viruses and immunohistochemistry to detect p53 expression in formaline-fixed, paraffin embedded blocks including 12 normal esophageal and 27 esophageal carcinoma specimens. HPV and EBV DNA were found in 25% and 0% of normal esophageal tissues and in 63% and 7% of esophageal carcinoma specimens, respectively. p53 expression was shown in 59% of esophageal carcinoma specimens only. HPV infection rate was significantly higher in specimens from carcinoma cases as compared with normal esophageal tissue obtained from cases without carcinoma. No correlation was found between p53 expression and/or the presence of viral DNA (HPV/EBV) in regard to the age and sex of the patient, histological grade, histological stage, depth of invasion, lymph node involvement, distant metastasis and the location of the tumors, p53 expression was almost equally distributed between HPV positive and negative carcinoma cases. Our results suggest that most of the esophageal carcinomas are associated with HPV infection and p53 mutations and there is no inverse correlation between HPV and infection and expression of p53 in esophageal carcinoma.

Characteristics of the in vitro propagation of the white sturgeon iridovirus (WSIV) were examined in 6 sturgeon cell lines. One new cell line originating from gonadal tissues (WSGO) produced up to 12-fold more WSIV [approximately 22 TCID50 (50% tissue culture infective dose) cell-1], than that of a previously established reference spleen cell line (WSS-2). Infected WSGO cell cultures were examined using phase microscopy, viral infectivity assay and transmission electron microscopy (TEM). At 15 degrees C, both mature virions and infectious virus were first detected after 7 d post-infection. Capsids acquired envelopes in the cytoplasm and virions remained primarily cell-associated during the 35 d replication cycle. Cellular changes including hyper-refractility and cytoplasmic swelling with dense cytoplasmic inclusions correlated to extensive proliferation of cytoplasmic vesicles and viral assembly sites. These cytological characteristics corresponded to changes in target cells of WSIV-infected juvenile white sturgeon following bath challenge. Microscopic changes in stained tissue sections of the host epithelium were detected 4 d post-challenge, approximately 8 d prior to the onset of clinical signs. Hypertrophied Malpighian cells surrounded by a prominent pericellular cisternum characterized epithelial lesions in the skin. Similar changes to epithelial cells of the barbels, olfactory organs and esophagus were also observed. Destruction of the sensory epithelium is suggested as a cause for cessation of feeding which occurs early in the infection of white sturgeon juveniles with WSIV.

In winter 1990, an adult male sea otter (Enhydra lutris) was found dead along the eastern shore of Prince William Sound, Alaska. Necropsy findings included an enlarged retained left testicle with a twisted spermatic cord, enlarged left sublumbar lymph node, emaciation, dental attrition, oral papules and ulcers, and luminal intestinal hemorrhage associated with numerous acanthocephalids. A malignant seminoma was present in the left testicle and left sublumbar lymph node. Additionally, herpesvirus like intranuclear inclusion bodies were found in oral, esophageal, and corneal epithelial cells. Virions consistent with a herpesvirus were found in esophageal epithelium. Dental attrition, severe intestinal acanthocephaliasis, the malignant seminoma, and emaciation were considered contributing factors in causing death. The herpesviral disease was probably secondary to the debilitation and stress. This is the first report of malignant seminoma with metastasis in a sea otter.

As the largest lymphoid organ and the largest reservoir of macrophages in the body, the gastrointestinal tract mucosa is probably the largest organ reservoir of macrophages infected with HIV-1. To elucidate the biology of HIV-1 infection of intestinal macrophages, we isolated lamina propria macrophages from normal human jejunum by neutral protease digestion, purified the cells by counterflow centrifugal elutriation, and then infected the cells with HIV-1. The lamina propria macrophages were permissive to macrophagetropic isolates of HIV-1 and substantially less permissive to lymphocyte-tropic isolates. Compared with blood monocytes, mucosal macrophages produced 2-3 logs less p24 antigen at peak infection. The reduced level of infection was not due to impaired macrophage viability, reduced CD4 expression, or the isolation procedure. These results confirm that macrophages isolated from the gastrointestinal tract mucosa can support HIV-1 production, albeit at a lower level than blood monocytes. The reduced level of virus production may reflect the unique biology of intestinal lamina propria macrophages.

The presence of human papillomavirus (HPV) DNA in esophageal brushings from human immunodeficiency virus (HIV)-seropositive hosts was investigated in a cross-sectional study. Oral and esophageal brushings from individuals scheduled for esophagogastroscopy (53 HIV-positive and 61 age-matched HIV-negative patients) were tested for the presence of HPV DNA by a consensus L1 polymerase chain reaction assay. HPV DNA was detected in esophageal brushings of 9 (17%) of the 53 HIV-seropositive patients and 0 of the 61 HIV-negative individuals. HPV-16 DNA was the most frequently detected. No proliferative mucosal lesion was noted in individuals with HPV-positive esophageal brushings. Cytological smears were done for 6 of the 9 patients with HPV-positive esophageal brushings, and epithelial atypia was recorded for 1. HIV infection and a history of genital herpes were strong independent predictors of HPV, suggesting that HPV is transmitted sexually in the esophagus.

Cattle persistently infected with foot-and-mouth disease virus were treated with dexamethasone to suppress the immune system in an attempt to influence the level of virus recovery from oesophageal pharyngeal (probang) samples. Twelve carrier cattle were assigned to one of three groups: control; 0.1 mg/kg dexamethasone; and 0.5 mg/kg dexamethasone. Groups 2 and 3 were injected intramuscularly three times weekly for 3 weeks with dexamethasone between days 33 and 56 post-infection with foot-and-mouth disease virus (FMDV). Cattle in both groups developed a leucocytosis, neutrophilia and lymphopenia. The secretory IgA response to FMDV infection was inhibited following, but not during, dexamethasone treatment between days 70 and 98 post-infection (P < 0.05). FMDV recovery from probang samples was reduced between days 40 and 64 post-infection (P < 0.05) during treatment with either 0.1 or 0.5 mg/kg dexamethasone. Following cessation of dosing with dexamethasone virus recovery returned to control levels. These observations suggest dexamethasone inhibits shedding of FMDV in a reversible manner which may be related to its immunosuppressive, anti-inflammatory or physiological actions.

A puppy suffering from chronic diarrhea was humanely killed at 90 days of age. Numerous Gram-negative bacilli were found adhering to the surface of as well as within epithelial cells from the stomach to the colon. Canine distemper virus inclusions were in the epithelial cytoplasm of the esophageal, gastric, and intestinal mucosa. Typical attaching and effacing ultrastructural lesions were in the stomach, and some bacilli were in the cytoplasm of the epithelial cells. Escherichia coli, isolated from the contents of the small intestine, belonged to serotype 0118: NM and were negative for plasmid-encoded EPEC adherence factor (EAF) and positive for the E. coli attaching effacing (eae) gene. Immunohistologically, bacilli attached to the epithelium from the stomach to the colon were positive for antisera against E. coli 0118. E. coli 0118: NM inoculated into human tissue culture cells (HEp-2 cells) were attached to the surface of the cells and within the cytoplasm. This is the first report of attaching and effacing E. coli (AEEC) infection in the stomach of the dog.

A free-living adult male gopher tortoise (Gopherus polyphemus) was found on Sanibel Island, Florida (USA), on 18 February 1992 with signs of upper respiratory disease. On necropsy after euthanasia on 27 February 1992, severe, extensive necrotizing ulcerative tracheitis, multifocal necrotizing pneumonia, and multifocal necrotizing ulcerative pharyngitis and esophagitis were observed. Large ovoid to round intracytoplasmic basophilic inclusions, which appeared to displace the nucleus to the cell periphery, occurred within degenerate and necrotic epithelial cells of the above tissues. On transmission electron microscopy of formalin-fixed trachea and lung, intracytoplasmic viral particles were observed within necrotic cells in the tracheal lumen and epithelial cells of the lung. Most infected cells also had a roughly spherical granular cytoplasmic inclusion that contained clusters of viral particles. Viral particles had an electron dense spherical to icosahedral core surrounded by a less electron dense icosahedral capsid. Mature extracellular virions were surrounded by an envelope and were 150 to 220 nm in diameter. Virions and cytoplasmic inclusions were morphologically similar to those of the Family Iridoviridae.

Background & Aims: Recent studies have suggested that esophageal human papillomavirus infection could be a risk factor for esophageal squamous cell carcinoma. The aim of this study was to evaluate the prevalence of human papillomavirus DNA sequences in the esophagus of French patients with esophageal squamous cell carcinoma., Methods: Multiplex polymerase chain reactions with consensus primers directed to the L1 gene or specific primers for human papillomavirus types 6, 11, 16, 18, 31, and 33 directed to E6 gene (40 cycles followed by restriction mapping of the amplified products) were used to determine the presence of human papillomavirus DNA sequences in esophageal squamous cell carcinoma (n = 75), normal adjacent mucosa (n = 49), and metastatic lymphadenopathies (n = 5). As an internal control, a target located in the embryonic myosin heavy-chain gene was used in each reaction., Results: Human papillomavirus DNA sequences could not be detected in any of the tumoral samples, the normal adjacent mucosa, or the metastatic lymphadenopathies., Conclusions: Human papillomavirus seems not to be implicated in esophageal carcinogenesis, at least in French patients, because the viral genomes are not associated with esophageal squamous cell carcinomas.