[Cervical infection epidemiology of human papillomavirus in Ushuaia, Argentina]. / Epidemiología de la infección cervical por virus papiloma humano en Ushuaia, Argentina.

Genital infection with human papillomavirus (HPV) is decisive in the causation of cervical cancer. In order to evaluate the epidemiology of HPV infection in Ushuaia, Province of Tierra del Fuego, Argentina, 132 endocervical cytobrushes from preneoplastic and neoplastic cases and controls were studied. Detection and typing of the viral genome was performed by polymerase chain reaction, combined with a restriction fragment length polymorphism assay or hybridization. The overall prevalence of HPV infection was 41% in the population examined, with a frequency of 26% in the controls and 71% in the cases under study. The 14-24 age group showed the highest HPV prevalence. The most common viral types in the infected population were HPV 16 (23%), HPV 18 (11%), HPV 33 (8%) and HPV 35 (8%), while high risk viral types were detected in 30% of the samples, 16% of the controls and 60% of the cases. This study provides the first data on the predominant viral types in Ushuaia. Our results show lower levels of infection than in regions with a high incidence of cervical cancer, HPV 16 being the most prevalent viral type. This research may be useful for selecting a specific vaccine targeting the population examined.

Epidemiología de la infección cervical por virus Papiloma humano en Ushuaia: Argentina / Cervical infection epidemiology of human papillomavirus in Ushuaia: Argentina

El virus Papiloma humano (HPV) es un factor necesario para el desarrollo del cáncer cervical. El objetivo del estudio fue conocer la epidemiología de dicha infección en Ushuaia, Provincia de Tierra del Fuego, Argentina. Se realizó un estudio de caso-control de 132 cepillados endocervicales. La detección y tipificación del genoma viral fue realizada por la reacción en cadena de la polimerasa, con posterior análisis de polimorfismos de fragmentos de restricción o hibridación. La prevalencia general de la infección fue 41%, correspondiendo 26% a los controles y 71% a los casos. El grupo etario con mayor prevalencia de HPV fue el de 14 a 24 años. Los tipos virales más frecuentes en la población infectada fueron HPV16 (23%), HPV18 (11%) y HPV33/35 (8% cada uno), resultando infectados con tipos virales de alto riesgo el 30% de las muestras, 16% de los controles y 60% de los casos. El trabajo aporta los primeros datos sobre los tipos virales predominantes en Ushuaia. Los resultados demostraron una prevalencia menor que en regiones con alta incidencia de cáncer cervical, siendo el HPV16 el más frecuente. La información obtenida permitiría estimar la efectividad de las vacunas en vías de aprobación, en la población estudiada.

Genital infection with human papillomavirus (HPV) is decisive in the causation of cervical cancer. In order to evaluate the epidemiology of HPV infection in Ushuaia, Province of Tierra del Fuego, Argentina, 132 endocervical cytobrushes from preneoplastic and neoplastic cases and controls were studied. Detection and typing of the viral genome was performed by polymerase chain reaction, combined with a restriction fragment length polymorphism assay or hybridization. The overall prevalence of HPV infection was 41% in the population examined, with a frequency of 26% in the controls and 71% in the cases under study. The 14-24 age group showed the highest HPV prevalence. The most common viral types in the infected population were HPV 16 (23%), HPV 18 (11%), HPV 33 (8%) and HPV 35 (8%), while high risk viral types were detected in 30% of the samples, 16% of the controls and 60% of the cases. This study provides the first data on the predominant viral types in Ushuaia. Our results show lower levels of infection than in regions with a high incidence of cervical cancer, HPV 16 being the most prevalent viral type. This research may be useful for selecting a specific vaccine targeting the population examined.

[Prevalence of cervical infection by human papilloma virus (HPV) in the Caucasian and Guaraní populations residing in the province of Misiones, Argentina]. / Prevalencia de la infección cervical por virus papiloma humano (HPV) en población caucásica y guaraní, residente en la provincia de Misiones, Argentina.

A genital infection with human papillomavirus (HPV) of a high risk type is necessary for the development of cervical carcinoma. HPV viral distribution among diverse world populations is not homogeneous, viral reservoirs having been detected in particular regions that can interact when humans engage in active contacts. Such viral dynamics alters the population cervical cancer relative risk, particularly when the prevalence of HPV oncogenic risk types is high. We have compared women exposed to different social, cultural and environmental conditions regarding cervical HPV infection, analyzing two populations from Misiones, Argentina: White urban women and--Guarani indian women living in the rain forest. Demographic, clinical and sexual behavior data were collected and cytological, colposcopical and virological analysis performed. Detection and genotypification of HPV was performed by PCR-RFLP. The prevalence for generic HPV infection found was high in both populations, urban women: 43%, Guarani indians: 60%, with a statistically significant difference. These values were positively associated to age of first intercourse, number of male partners and smoking history. HPV type-specific prevalences showed a relative homogeneity between populations when the main representatives of the high risk (16 and 18: 23%) and low risk (6 y 11: 12%) types were grouped together. However, the presence of other viral types was notoriously different, representing only 9% in urban women and 29% in Guarani indians with particularly high risk HPV types (33, 35, 39, 45, 51, 52, 58, 67, 68). This situation might be of importance for future viral dynamics, phylogenetic and vaccine formulation studies.

Prevalencia de la infección cervical por virus papiloma humano (HPV) en población caucásica y guaraní, residente en la provincia de Misiones, Argentina / [Prevalence of cervical infection by human papilloma virus (HPV) in the Caucasian and Guaraní populations residing in the province of Misiones, Argentina]

A genital infection with human papillomavirus (HPV) of a high risk type is necessary for the development of cervical carcinoma. HPV viral distribution among diverse world populations is not homogeneous, viral reservoirs having been detected in particular regions that can interact when humans engage in active contacts. Such viral dynamics alters the population cervical cancer relative risk, particularly when the prevalence of HPV oncogenic risk types is high. We have compared women exposed to different social, cultural and environmental conditions regarding cervical HPV infection, analyzing two populations from Misiones, Argentina: White urban women and--Guarani indian women living in the rain forest. Demographic, clinical and sexual behavior data were collected and cytological, colposcopical and virological analysis performed. Detection and genotypification of HPV was performed by PCR-RFLP. The prevalence for generic HPV infection found was high in both populations, urban women: 43

, with a statistically significant difference. These values were positively associated to age of first intercourse, number of male partners and smoking history. HPV type-specific prevalences showed a relative homogeneity between populations when the main representatives of the high risk (16 and 18: 23

) types were grouped together. However, the presence of other viral types was notoriously different, representing only 9

in urban women and 29

in Guarani indians with particularly high risk HPV types (33, 35, 39, 45, 51, 52, 58, 67, 68). This situation might be of importance for future viral dynamics, phylogenetic and vaccine formulation studies.

) and low risk (6 y 11: 12

Prevalencia de la infección cervical por virus papiloma humano (HPV) en población caucásica y guaraní, residente en la provincia de Misiones, Argentina. / [Prevalence of cervical infection by human papilloma virus (HPV) in the Caucasian and Guaraní populations residing in the province of Misiones, Argentina]

A genital infection with human papillomavirus (HPV) of a high risk type is necessary for the development of cervical carcinoma. HPV viral distribution among diverse world populations is not homogeneous, viral reservoirs having been detected in particular regions that can interact when humans engage in active contacts. Such viral dynamics alters the population cervical cancer relative risk, particularly when the prevalence of HPV oncogenic risk types is high. We have compared women exposed to different social, cultural and environmental conditions regarding cervical HPV infection, analyzing two populations from Misiones, Argentina: White urban women and--Guarani indian women living in the rain forest. Demographic, clinical and sexual behavior data were collected and cytological, colposcopical and virological analysis performed. Detection and genotypification of HPV was performed by PCR-RFLP. The prevalence for generic HPV infection found was high in both populations, urban women: 43

, Guarani indians: 60

, with a statistically significant difference. These values were positively associated to age of first intercourse, number of male partners and smoking history. HPV type-specific prevalences showed a relative homogeneity between populations when the main representatives of the high risk (16 and 18: 23

) and low risk (6 y 11: 12

) types were grouped together. However, the presence of other viral types was notoriously different, representing only 9

in urban women and 29

in Guarani indians with particularly high risk HPV types (33, 35, 39, 45, 51, 52, 58, 67, 68). This situation might be of importance for future viral dynamics, phylogenetic and vaccine formulation studies.

Physical status of the E2 human papilloma virus 16 viral gene in cervical preneoplastic and neoplastic lesions.

BACKGROUND: Integration of human papilloma virus (HPV) 16 DNA is considered an important genetic change in cervical lesion progression towards ICC. The viral E2 gene is often disrupted by this process, releasing suppression of viral E6/E7 oncogenes, a key factor for oncogenic progression. OBJECTIVES: To evaluate the physical status of HPV 16 E2 gene in cervical preneoplastic and neoplastic lesions and its relation with lesion severity. STUDY DESIGN: A sensitive PCR approach for the detection of an intact E2 HPV 16 gene in infected epithelial cells from the cervix with low grade squamous intraepithelial lesion (LGSIL), high grade squamous intraepithelial lesion (HGSIL) and invasive cervical carcinoma (ICC) diagnosis was applied. The correlation between gene disruption and lesion stage was examined. RESULTS: Sixty-two LGSIL, 39 HGSIL and 24 ICC samples were analyzed. Fifty-seven LGSIL [92%], 13 HGSIL [33%] and 4 ICC [17%] showed results compatible with an intact E2 gene, while 5 LGSIL [8%], 26 HGSIL [67%] and 20 ICC [83%] samples gave no signal. CONCLUSIONS: HPV 16 E2 gene disruption showed a positive correlation with cervical lesion progression, particularly from LGSIL to HGSIL. Although additional genetic events are very likely to be needed for HGSIL to ICC progression, the E2 gene disruption is a putative early marker to consider in the prognostic analysis of HPV 16 chronically infected women.

Human papillomavirus (HPV) DNA in penile carcinomas in Argentina: analysis of primary tumors and lymph nodes.

Among sexually transmitted diseases, infection by human papillomavirus (HPV) has become one of the most important. On the other hand, though epidemiological data show that some HPV types are closely associated with cervical cancer, few reports have been found with reference to penile carcinoma because of its rare occurrence. The aim of this study was to investigate the relationship between HPV infection and penile cancer in Argentina. A retrospective study was carried out on 38 white men with penile squamous-cell carcinoma. Sixty-five archival fixed biopsies taken from 34 primary penile tumors, 25 nodal metastases, 1 skin "satellite" metastasis and 5 histologically normal lymph nodes were used as specimens. HPV detection and typing were carried out by the polymerase chain reaction (PCR) using generic primers, combined with single-stranded conformational polymorphism (SSCP) analysis. HPV DNA was found in 71% patients, corresponding 81% of them to "high risk" types, with predominance of HPV 18. Both primary tumors and metastases showed concordance of HPV occurrence and type in both lesions. In 3 patients, HPV 16 was detected not only in primary tumors and metastases, but also in histologically normal lymph nodes. Our data indicate that most penile carcinomas in Argentine patients are etiologically related to HPV, especially to "high risk" genital types. The agreement in HPV detection between primary tumors and metastases suggests a potential viral role in tumor progression. HPV detection in otherwise histologically normal lymph nodes might be useful as early marker of a metastatic process.

[Molecular variants of human papillomavirus (HPV) types 16 and 18 in adenocarcinomas of the cervix]. / Variantes moleculares de virus papiloma humano (HPV) tipos 16 y 18 en adenocarcinomas de cérvix.

Human Papillomavirus (HPV), placebo clinical trial particularly types 16 and 18, are considered human carcinogens since an etiological association has been demonstrated between these viruses and the development of cervical cancer. While the viral role in squamous carcinoma has been largely studied, the information available on adenocarcinoma is scarce, partly because of its lower frequency. In this paper we investigated the presence of HPV types and intratype variants in adenocarcinomas of the cervix. A total of 23 archive samples, fixed and paraffin embedded biopsies, were included. The detection and viral typing was performed by generic PCR and subsequent single stranded conformational polymorphism analysis (SSCP). Genetic variability was investigated in a 450 bp-fragment corresponding to L1 gene by post-PCR direct sequencing. We detected 11 HPV 16 positive samples (9 prototypes and 2 variants: 1 European and 1 Asiatic-American), 10 HPV 18 (9 prototypes and 1 European variant), 1 HPV 31 and 1 negative. The high risk HPV association with this neoplasia was confirmed with a high prevalence (43%) of HPV 18, (but) without predominance over the other types as previously published. The demonstrated variability in L1 protein epitopes originated aminoacidic changes which could have implications on the immune response and therefore should be considered in a vaccine design.

[Ha-ras and p53 gene mutations scanned by PCR-SSCP in premalignant and malignant lesions of the uterine cervix associated with human papillomavirus]. / Mutaciones en genes Ha-ras y p53 detectadas mediante PCR-SSCP en lesiones premalignas y malignas de cuello uterino asociadas con virus papiloma humano.

The aim of this study w trial randomized as to investigate the frequencies of human papillomavirus (HPV) and mutation in Ha-ras oncogene and tumour suppressor p53 gene in cervical cancer and precursor lesions. A total of 30 invasive carcinomas (IC), 36 cervical intraepithelial neoplasia grade III (CIN III) and 12 normal tissues adjacent to the tumor (NT) were included. HPV typification and scanning of possible mutations in Ha-ras and p 53 genes were made by SSCP-PCR. The IC cases showed 93% HPV positivity, 41% having mobility shifts for Ha-ras mutations and 17% for p53 mutations while in CIN III, these percentages were 80%, 18% and 11%, respectively. In normal tissues HPV frequency was 17%. All Ha-ras mutated samples were HPV positive but 33% of p53 mutated cases were HPV negative. All mutations were heterozygous. HPV 16 was more prevalent (44%) than HPV 18 (15%) and the high rate of undetermined HPV types (18%) would indicate the circulation in our country of other types different from the assayed HPV controls (6, 11, 16, 18, 31 and 33), being variants or mixed infections. The low frequency of p53 mutations (17%) strengthens the view that wild type p53 inactivation by HPV probably plays a major role in the pathogenesis of cervical cancer. Because mutated Ha-ras was found in HPV associated premalignant lesions, we speculate that it represents an early marker for progression. Our findings provide additional evidence for an interactive effect between high risk types of HPV and oncogene activation in the development of uterine cervical cancer.

Variantes moleculares de virus papiloma humano (HPV) tipos 16 y 18 en adenocarcinomas de cérvix. / [Molecular variants of human papillomavirus (HPV) types 16 and 18 in adenocarcinomas of the cervix]

Human Papillomavirus (HPV), placebo clinical trial particularly types 16 and 18, are considered human carcinogens since an etiological association has been demonstrated between these viruses and the development of cervical cancer. While the viral role in squamous carcinoma has been largely studied, the information available on adenocarcinoma is scarce, partly because of its lower frequency. In this paper we investigated the presence of HPV types and intratype variants in adenocarcinomas of the cervix. A total of 23 archive samples, fixed and paraffin embedded biopsies, were included. The detection and viral typing was performed by generic PCR and subsequent single stranded conformational polymorphism analysis (SSCP). Genetic variability was investigated in a 450 bp-fragment corresponding to L1 gene by post-PCR direct sequencing. We detected 11 HPV 16 positive samples (9 prototypes and 2 variants: 1 European and 1 Asiatic-American), 10 HPV 18 (9 prototypes and 1 European variant), 1 HPV 31 and 1 negative. The high risk HPV association with this neoplasia was confirmed with a high prevalence (43

) of HPV 18, (but) without predominance over the other types as previously published. The demonstrated variability in L1 protein epitopes originated aminoacidic changes which could have implications on the immune response and therefore should be considered in a vaccine design.

Mutaciones en genes Ha-ras y p53 detectadas mediante PCR-SSCP en lesiones premalignas y malignas de cuello uterino asociadas con virus papiloma humano. / [Ha-ras and p53 gene mutations scanned by PCR-SSCP in premalignant and malignant lesions of the uterine cervix associated with human papillomavirus]

The aim of this study w trial randomized as to investigate the frequencies of human papillomavirus (HPV) and mutation in Ha-ras oncogene and tumour suppressor p53 gene in cervical cancer and precursor lesions. A total of 30 invasive carcinomas (IC), 36 cervical intraepithelial neoplasia grade III (CIN III) and 12 normal tissues adjacent to the tumor (NT) were included. HPV typification and scanning of possible mutations in Ha-ras and p 53 genes were made by SSCP-PCR. The IC cases showed 93

HPV positivity, 41

having mobility shifts for Ha-ras mutations and 17

for p53 mutations while in CIN III, these percentages were 80

, 18

and 11

, respectively. In normal tissues HPV frequency was 17

. All Ha-ras mutated samples were HPV positive but 33

of p53 mutated cases were HPV negative. All mutations were heterozygous. HPV 16 was more prevalent (44

) than HPV 18 (15

) and the high rate of undetermined HPV types (18

) would indicate the circulation in our country of other types different from the assayed HPV controls (6, 11, 16, 18, 31 and 33), being variants or mixed infections. The low frequency of p53 mutations (17

) strengthens the view that wild type p53 inactivation by HPV probably plays a major role in the pathogenesis of cervical cancer. Because mutated Ha-ras was found in HPV associated premalignant lesions, we speculate that it represents an early marker for progression. Our findings provide additional evidence for an interactive effect between high risk types of HPV and oncogene activation in the development of uterine cervical cancer.

Human papillomavirus cervical infection and associated risk factors in a region of Argentina with a high incidence of cervical carcinoma.

OBJECTIVE: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV) cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer. METHODS: A case-control study of 330 women participating in a cervical cytological screening program conducted in Posadas city, Misiones, Argentina, from February 1997 to November 1998 was carried out. Standardized questionnaires were administered, and clinical examination including colposcopy was performed. Fresh endocervical specimens for HPV DNA detection by generic polymerase chain reaction were collected and the products typed by dot-blot hybridization. RESULTS: Human papillomavirus DNA was found in 61% of samples analyzed (185/301). Samples with normal cytology had a 43% infection rate (85/199), while those classified as low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive cervical carcinoma had an infection rate of 96% (53/55), 100% (29/29), and 100% (18/18), respectively. Human papillomavirus typing showed a 64% (118/185) prevalence of type 16 among all the infected population analyzed; type 16 was detected among 49% (42/85) of infected samples with normal cytology and in an average of 74% (74/100) with abnormal cytology. Sexual behavior, residence in southern Paraguay, and history of a previous sexually transmitted diseases were the main risk factors associated with high-grade cervical lesions. CONCLUSIONS: An elevated prevalence of HPV infection was detected in this population, which also has a high incidence of cervical cancer. The broad distribution of high-risk HPV type 16 in women with normal cytology and colposcopy suggests that viral infection is an important determinant of regional cancer incidence.

Persistence of human papillomavirus DNA in cervical lesions after treatment with diathermic large loop excision.

OBJECTIVE: The aim of this study was to identify human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions and to evaluate the persistence of viral DNA after diathermic large loop excision (DLLE) treatment. STUDY DESIGN: Biopsies from 36 patients with low- and high-grade CIN lesions were studied before and after DLLE treatment looking for HPV sequences. DNA was extracted to perform a radioactive polymerase chain reaction (PCR) using GP 5,6 generic primers. PCR products were analyzed by the single-stranded conformational polymorphism (SSCP) which is a simultaneous detection and typing method. Dot-blot hybridization with generic and type-specific biotinylated oligonucleotide probes was applied in some cases. RESULTS: HPV DNA was found in all pretreatment samples, and the viral type was identified in 80% of them, HPV 16 being the most prevalent. The viral type coincided with that detected in the first biopsy in all except one case. Seventy five percent of the patients (27 cases) were negative for CIN at follow up, but 50% of them remained HPV DNA positive. CONCLUSION: DLLE treatment was effective in removing the CIN lesion but not the HPV. This fact points out the need to asses the presence of HPV in DNA during the follow-up, since viral persistence has been considered a high risk factor for recurrence and/or malignant transformation.

Mecanismos de oncogénesis viral / Mechanisms of viral oncogenesis

Actualmente se sabe que el 20 por ciento de los cánceres humanos están asociados con virus oncogénicos. El virus papiloma humano con cáncer anogenital, los virus de la hepatitis B y C con carcinoma hepatocelular, el virus Epstein Barr con carcinomas nasofaríngeos y linfomas, el virus de la leucemia-linfoma T con leucemias en el adulto. Un rasgo común en todos los tumores asociados con infección viral es el largo período de latencia entre la infección y la aparición de la neoplasia y la baja proporción de individuos infectados que desarrollan un tumor maligno. Estas observaciones indican que los virus oncogénicos son necesarios pero no suficientes para inducir cáncer, otros factores podrían estar involucrados. Esta actualización resume informaciones recientes acerca de los mecanismos de carcinogénesis viral, en particular, la interacción de oncoproteínas virales y proteínas supresoras tumorales. La inactivación de estas proteínas supresoras podría representar una estrategia común a través de la cual los virus tumorales pueden contribuir a la transformación maligna de la célula (AU)

Mecanismos de oncogénesis viral / Mechanisms of viral oncogenesis

Actualmente se sabe que el 20 por ciento de los cánceres humanos están asociados con virus oncogénicos. El virus papiloma humano con cáncer anogenital, los virus de la hepatitis B y C con carcinoma hepatocelular, el virus Epstein Barr con carcinomas nasofaríngeos y linfomas, el virus de la leucemia-linfoma T con leucemias en el adulto. Un rasgo común en todos los tumores asociados con infección viral es el largo período de latencia entre la infección y la aparición de la neoplasia y la baja proporción de individuos infectados que desarrollan un tumor maligno. Estas observaciones indican que los virus oncogénicos son necesarios pero no suficientes para inducir cáncer, otros factores podrían estar involucrados. Esta actualización resume informaciones recientes acerca de los mecanismos de carcinogénesis viral, en particular, la interacción de oncoproteínas virales y proteínas supresoras tumorales. La inactivación de estas proteínas supresoras podría representar una estrategia común a través de la cual los virus tumorales pueden contribuir a la transformación maligna de la célula

A novel human papillomavirus sequence from an international cervical cancer study.

Novel human papillomaviruses (HPVs) were sought as part of a recent international study of > 1000 invasive cervical carcinomas. A single novel HPV designated IS39 was identified in this study. IS39 is most closely related to another novel virus, W13B (MM4), variants of W13B (MM4), and HPV-51.

Effect of human papillomavirus infection on estrogen receptor and heat shock protein hsp27 phenotype in human cervix and vagina.

In this study we have explored whether, as a consequence of human papillomavirus (HPV) infection, there is inappropriate expression of estrogen receptor and/or of a small heat shock protein of 27,000 daltons (hsp27). Estrogen receptor, hsp27, and HPV structural antigens were detected by immunocytochemistry, while HPV DNA (6/11, 16/18, 31/35/51) was determined by in situ hybridization in cervical and vaginal samples from 40 patients. Most of the samples with HPV infection without atypia showed a shift in estrogen receptor expression since this protein appeared mainly in the intermediate and superficial cell layers. In the serial sections, these layers displayed strong estrogen receptor staining, together with high HPV replication and late HPV gene expression. In the samples with HPV infection and atypia, estrogen receptors were also frequently found in the basal and parabasal cells, but almost 20% of these samples did not show estrogen receptors. The presence of high estrogen receptor expression was not dependent on a particular HPV DNA type. On the other hand, interesting modifications in hsp27 expression were observed in the HPV-infected tissues. The cytoplasm of the cells with koilocytotic changes showed very low hsp27 content. In several samples this protein appeared in the nuclei of the superficial cells, and sometimes it was also observed in the cytoplasm of the basal cells. These changes in estrogen receptor and hsp27 expression suggest that these proteins might have a role in virus-host biology.

Circulating interferon in the guinea pig infected with the XJ, prototype Junin virus strain.

The interferon (IFN) induction capacity of the XJ prototype strain of Junín virus (JV) was investigated in the guinea pig model. Circulating alpha IFN was detected in 50% of the animals from days 2 to 9 postinfection (pi) and in 100% at day 11 pi, when all animals were in the premortem stage. Individual levels ranged from 20 to 1,280 guinea pig IFN units (GPIFNU)/ml. A correlation between XJ strain virulence and IFN titers was recorded. A possible role of IFN as a pathogenic factor in the outcome of the disease is discussed.

Interferon response in the guinea pig infected with Junín virus.

The "in vivo" interferon (IFN) induction capacity of two Junín virus strains--the attenuated XJCl3 and the intermediate virulent MC2--was studied in the guinea pig experimental model. Three different doses of XJCl3 strain--2,000, 10,000, and 50,000 TCID50--and a single dose of 10,000 TCID50 of MC2 were assayed. Animals were bled from day 0 to day 14 postinjection (pi) XJCl3 groups showed a constant serum IFN response. MC2 infection showed that 16% of the animals failed to develop interferonemia. The IFN activity was alpha type in most cases. The IFN serum levels induced by the MC2 strain were always lower than those attained after XJCl3 infection. The response to the positive control assayed, Newcastle disease virus, was higher and earlier than that obtained for Junín virus strains. The highest IFN individual value, which induced 160 guinea pig IFN U/ml, was detected at day 2 following XJCl3 infection, and corresponded to the highest XJCl3 dose assayed. Average values ranged from 23 to 65 guinea pig IFN U/ml, for XJCl3 groups and 15 guinea pig IFN U/ml for the MC2 group, measured at the day of maximal response. IFN presence was studied in homogenates from brain, spleen, and lymph nodes; it was detected in organs from guinea pigs infected with XJCl3 but not in organs from MC2 infected animals. IFN levels in sera or in organs failed to correlate with the histological findings. Demonstration of viral antigens in organs of infected animals, and seroconversion of Junín virus (JV) confirmed the evolution of the disease. A significant weight loss was observed just after serum IFN disappearance.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro immune interferon induction during tumor evolution.

In a syngeneic C3H mammary adenocarcinoma model we studied gamma-interferon (gamma IFN) production during tumor evolution. The IFN production was induced by soluble tumor extracts on spleen cell cultures from tumor-bearing mice. A low level of IFN production was found in culture supernatants from small tumor-bearing mice (tumor diameter less than 10 mm, 12-15 days of tumor evolution). In advanced stages of tumor growth (diameter more than 15 mm, 20 days or more of tumor evolution), this ability was lost.