Mouse mammary tumor virus (MMTV) infection in SWISS and RIII mice

Summary Host-virus relationships were examined in mice from the two mouse mammary tumor virus (MMTV)-infected strains SWISS MB+ and RIII, which harbour the same MMTV variant, and from the derived sublines Swiss MB-and RIIIf, which were freed of milk-borne MMTV by foster-nursing. These two strains are not phylogenetically related, the SWISS strain bearing the endogenousMtv-3 locus in its DNA. In RIII and SWISS MB+ mice, the incidence of early mammary tumors, which was of 96% and 8%, respectively, was correlated to the level of MMTV expression in milk. In the SWISS MB-line, a non-coordinate expression of the provirus associated with theMtv-3 locus was observed in the mammary glands, the salivary glands and the spleen. This expression was not tumorigenic and was characterized by the presence of the p28gag antigen and the absence of the gp52env antigen, except, however, in mammary glands of elder mice where traces of gp52 were found. In the mammary glands of SWISS MB+ mice, the expression of theMtv-3 locus was masked by large amounts of antigens resulting from exogenous virus expression. RIIIf mice were MMTV-negative.Viral antigens coexisted with anti-MMTV antibodies in the serum of infected and tumor-bearing mice, but not in the form of immune complexes as verified by a method that allowed to detect specific antigen-containing-soluble immune complexes. An anti-MMTV serum reactivity was also detected in SWISS MB-and RIIIf mice. However, the serum response was higher in the two SWISS lines than in the two RIII lines. Except in tumor-bearing mice, the anti-MMTV response was not significantly modified by the presence of exogenous virus and thus resulted essentially from exposure to endogenous MMTV expression. In experimental infection studies, RIII mice were more susceptible to MMTV infection than SWISS mice. The correlation between resistance to MMTV infection and serum response to endogenous MMTV expression, suggests that the non-tumorigenic expression of an endogenous provirus can protect at least partially, against exogenous MMTV infection.     

Human breast cancer and lymphomas may share a common aetiology involving Mouse Mammary Tumour Virus (MMTV)

Mouse Mammary Tumour Virus (MMTV) causes breast tumours in mice, and has been implicated in the aetiology of murine lymphomas. Several recent human studies have detected MMTV-env DNA sequences in 30-40% of tumours from breast cancer patients but in less than 4% of normal breast tissue. MMTV DNA has been detected in simultaneously diagnosed primary lymphoma and breast cancer tissue, suggesting MMTV may be involved in the aetiology of both breast cancer and lymphoma. We further hypothesize that if lymphoma and breast cancer are both associated with a common aetiologic virus then women with prior lymphoma may have an increased risk of breast cancer and vice versa. Despite the significant increase in the incidence of both lymphoma and breast cancer over the last few decades, their aetiologies are not well understood. Intriguing evidence to date suggests that the aetiology of a subgroup of human breast cancers and lymphomas may have viral involvement, and this warrants further investigation.     

Coexistence of the mouse mammary tumor virus (MMTV) major glycoprotein and natural antibodies to MMTV in sera of mammary tumor-bearing mice.

Sera of mammary tumor-bearing mice contain the major envelope glycoprotein (gp52) of mouse mammary tumor virus (MMTV) and autogenous antibodies to MMTV. Although antibodies to MMTV are readily demonstrable in sera of both tumor-free and tumorbearing animals, detection of the viral glycoprotein appears to be dependent on the presence of a palpable mammary tumor. MMTV gp52 was detected both as the free protein and in a high molecular weight complex as demonstrated by velocity sedimentation centrifugation. MMTV gp52 was also detected in both mammary tissue and lymph nodes of female C3H/HeN mice. The reproductive organs of the male C3H/HeN mice, such as the vas deferens and vesicular, coagulating, and prostate glands, contained gp52, while no MMTV gp52 could be demonstrated in the testes, epididymis, or preputial glands. This antigen was not found in any tissues of male or female BALB/c mice.     

荧光定量PCR法检测母乳巨细胞病毒感染和母婴传播

目的了解母乳人巨细胞病毒（HCMV）感染状况和母婴传播情况.方法应用荧光定量PCR（FQ-PCR）法检测390份母乳中HCMV-DNA含量,其中236份母乳配对与患儿血液或尿液中HCMV-DNA含量作一定分析.结果可疑或确诊HCMV感染患儿母亲母乳HCMV-DNA阳性率达71.28%,HCMV-DNA阳性母乳喂养的婴儿,其血或尿HCMV-DNA阳性率明显高于HCMV-DNA阴性母乳喂养的婴儿.结论HCMV感染母乳是婴儿获得性感染的主要途径.     

Generation of a mouse mammary tumor virus (MMTV) pseudotype of Kirsten sarcoma virus and restriction of MMTV gag expression in heterologous infected cells.

C3H mouse mammary tumor cells producing mouse mammary tumor virus (MMTV) were cocultivated with nonproducer mouse cells (KNIH) transformed by Kirsten sarcoma virus (KiSV). These cocultivated cells were then treated with mitomycin C and overlayed onto human embryonic skin and muscle cells. The virus resulting from this cocultivation could be titrated in a focus-forming assay on Fischer rat embryo (FRE) cells exhibiting one-hit kinetics. Furthermore, focus formation on FRE cells was neutralized specifically by antiserum directed against MMTV and the major MMTV external glycoprotein gp52, but not against a broadly reactive antiserum directed murine leukemia virus (MuLV) gp70 and MMTV gp36, p27, p14, and p10. These results demonstrate the generation of a KiSV(MMTV) pseudotype and further demonstrate that gp52 is a target antigen for neutralization of MMTV. This pseudotype possessed a wide host range, transforming cells of human, rat, mouse, mink, and rabbit origin. MMTV but not MuLV antigen expression was demonstrated in the KiSV(MMTV) pseudotype-infected cells. Analysis of intracellular MMTV protein synthesis in these in vitro-infected cells has indicated that the low yield of extracellular MMTV produced by the transformed cells may be the result of the poor expression of the MMTV gag precursor polyprotein relative to the expression of the env gene polyprotein. These studies thus provide the basis for an in vitro infectivity assay for neutralization and host range studies of MMTV.     

Natural infection of ducks with Mycoplasma synoviae and Mycoplasma gallisepticum and Mycoplasma egg transmission

Mycoplasma gallisepticum (MG), M. synoviae (MS), M. cloacale (MC) and M. anatis were isolated from ducks kept in a yard in close contact with chickens that were infected with MG, MS and some other avian Mycoplasma species. MG, MS and MC were isolated also from embryonated duck eggs and from infertile duck eggs laid during the first four weeks of egg production. Infected ducks did not show clinical signs of MG or MS infection in chicken. Detectable MG and MS agglutinating antibodies were not present in duck sera. However, they were found in two yolks of 10 tested from embryonated eggs. In the haemagglutination - inhibition (HI) tests yolks from embryonated eggs yielded significantly higher (P<0.01) titres of MS antibodies than duck sera. Geometric mean value of MS HI titres in tested duck sera was 20, while those of yolks from embryonated eggs was 333. It is probably the first report concerning isolation of MS from the naturally infected ducks and furthermore, concerning isolation of MG, MS and MC from naturally infected embryonated eggs.     

Characterization of RNA Synthesis and Translation of Bovine Viral Diarrhea Virus (BVDV)

Full length and replicon genomes of various strains of bovine viral diarrhea virus (BVDV) have been characterized. Analysis of growth kinetics for a pair of cytopathogenic (cp) and noncytopathogenic (ncp) strains revealed that ncp strain synthesized viral RNA at much reduced level compared to the cp strain. Kinetics of translation and replication, the effects of bi-cistronic versus mono-cistronic genomes, and cis requirements for viral replication were also examined in a BVDV replicon DI9c. Importantly, our results suggest a tight regulation and a switch from translation to replication, and demonstrated the cis requirements of NS4B and NS5A in replication.     

Experimental infection in mice with larvae of Baylisascaris transfuga (Nematoda)

B. transfuga larvae migrated in livers, lungs and brains of experimentally infected mice. B. transfuga larvae have never been reported as etiologic agents of visceral larva migrans, but our results show that they have a migration in experimental paratenic hosts of a type that suggests their possible role in this syndrome.     

Mouse hepatitis virus and host determinants of vertical transmission and maternally-derived passive immunity in mice

Summary Transmission of mouse hepatitis virus (MHV) in utero following oronasal inoculation of pregnant mice was found to depend upon MHV strain and host genotype. Virulent, polytropic MHV-JHM was recovered from multiple maternal tissues, including liver and uterus, as well as placenta and fetus in susceptible BALB/cByJ mice. Fetuses were infected during all 3 trimesters of pregnancy. Low virulence, polytropic MHV-S infected fetuses in a low percentage of susceptible BALB/cByJ dams. Infection of resistant CD-1 mice with MHV-JHM was limited, with no fetal infection. Enterotropic MHV-Y was largely restricted to intestine of BALB/cByJ and CD-1 dams, with minimal dissemination and no fetal infection. Maternally-derived MHV IgG antibody was detectable in pup sera through 4 weeks of age. Antibody titers were generally lower in second litters of the same dam. Cross-fostering experiments showed that antibody was transferred via colostrum and not in utero, and that pups were capable of absorption through 2 weeks of age. Pups nursing immune dams were protected against MHV challenge at 1 and 2 weeks of age, compared to pups nursing naive dams. Immunity to MHV challenge was cross-protective against both antigenically homotypic and heterotypic strains of MHV.     

DMBA诱导的肝脏特异性IGF-1基因缺失鼠原发性乳腺癌的组织学特征

目的探讨血清中胰岛素样生长因子-1(IGF-1)水平与乳腺肿瘤发生过程中组织学改变的关系。方法实验中所用的肝脏特异性IGF-1基因缺失(LID)小鼠,其循环中IGF-1水平仅为正常小鼠(对照组小鼠)的25％。管饲化学致癌剂7,12-二甲基苯蒽(DMBA)诱导产生原发性乳腺癌。结果对照组肿瘤晚期可见广泛的鳞状上皮化生,而LID鼠肿瘤晚期出现广泛增生,极少出现化生。与对照组相比,鼠乳腺肿瘤的潜伏期均明显延长,LID小鼠可触及的乳腺肿瘤发病率明显下降,其肿瘤的出现也明显延迟。结论在致癌剂DMBA诱导的乳腺肿瘤模型中,IGF-1水平决定了乳腺肿瘤发生的组织学类型。     

Natural infection of geese with Mycoplasma gallisepticum and Mycoplasma synoviae and egg transmission of the mycoplasmas

Mycoplasma gallisepticum (MG) and M. synoviae (MS) were isolated from geese kept for more than a year on a multiple-age chicken farm. Agglutinating antibodies against MG and MS were found in the sera of some geese which were positive also in the haemagglutination-inhibition tests. The isolation of MG and MS from several organs of goose embryos indicates that egg transmission occurs. It is probably the first report concerning isolation of MS from the naturally infected geese and furthermore concerning isolation of MG and MS from naturally infected goose embryos.     

Susceptibility of mouse mammary glands to murine gammaherpesvirus 72 (MHV-72) infection: evidence of MHV-72 transmission via breast milk.

Murine gammaherpesvirus 72 (MHV-72) is a virus of wild rodents and serves as a convenient small animal model to understand the pathogenesis of Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV8) infection. In laboratory mice MHV-72 causes an acute infection of lung epithelial cells and establishes the latency in B lymphocytes. In this study, we investigated athymic nude and immunocompetent mice for distribution of virus in organs after infection with MHV-72. Ten days following subcutaneous dorsal injection of nude mice, virus replicated in lungs, lymphoid organs, salivary glands and also in mammary glands. The virus titre decreased by day 21 post-infection in former tissues, but increased in mammary glands. Presence of virus DNA sequences was detected in the lymphoid and non-lymphoid tissues until the death of the animals (about 1 month post-infection). Infection of immunocompetent mice with MHV-72 induced replication of virus up to 42 days post-infection in mammary glands reaching the highest level of infectious virus at day 8 post-infection. These data show that there is latent infection in mice never detected before. Moreover, virus DNA was detected using nested PCR (by amplification of a portion of gp150 gene sequence) in the mammary glands and the milk of mouse mothers infected with MHV-72 2 days before delivery. We demonstrated the presence of virus DNA also in the milk removed from the stomach of non-infected newborn mice, which were nourished by infected mothers (wet-nurses) for 1 or 2 days. The failure to detect the virus DNA in newborn mice lungs confirmed that they did not become infected from wet-nurses by the intranasal route. This suggests that MHV may be naturally transmitted to newborn mice via breast milk.