Evidence Of Virus Infection Research Articles

Dilated cardiomyopathy in children: Review of all presentations to a children's hospital over a 5-year period and the impact of family cardiac screening.

This study aims to report the aetiology and outcome of dilated cardiomyopathy (DCM) in children from New Zealand and to assess the outcome of protocolised family cardiac investigation introduced in 2007. Retrospective review of all patients with DCM, aged <15 years, presenting to the children's hospital between 01/01/2007 and 01/03/2012. Oncology patients were excluded. Family screening results were assessed. Thirty-five patients were identified. Median age 1 year: 26/35 (74%) <5 years. Ethnicity: New Zealand European 14/35 (40%), Maori 11/35 (31%), Pacific Island 5/35 (14%) and other 5/35(14%). Excluding the four cases with biopsy-proven myocarditis, family cardiac screening was documented in 15/31 (48%). Of these, 7/15 (47%) had a positive family screen. Six previously undiagnosed DCM cases were found in these families. Five of the seven familial DCM cases had evidence of viral infection at presentation. Final aetiology: Myocarditis, 15/35 (43%), with Parvovirus being the commonest virus identified 10/15(67%). Familial, seven (20%), Idiopathic, seven (20%), Others, six (17%). Overall outcome was death 10/35(28%), ongoing dysfunction 16/35 (46%) and normalisation in 9/35 (26%). The median time to death from diagnosis was 1.5 months (3 days to 3 years). Death occurred in 4/7 with familial DCM (57%) compared with 6/28 (21%) among the others (ns). Recovery occurred in 0/7 with familial DCM versus 4/4 with biopsy proven myocarditis (P < 0.05). Almost half of families screened had evidence of familial DCM, and these children carried a worse prognosis. Maori and Pacific Island children seem to be over-represented. Family investigation led to the identification of many pre-symptomatic individuals even when viral aetiology was suspected initially.

Avian influenza virus ecology in Iceland shorebirds: Intercontinental reassortment and movement

Shorebirds are a primary reservoir of avian influenza viruses (AIV). We conducted surveillance studies in Iceland shorebird populations for 3years, documenting high serological evidence of AIV exposure in shorebirds, primarily in Ruddy Turnstones (Arenaria interpres; seroprevalence=75%). However, little evidence of virus infection was found in these shorebird populations and only two turnstone AIVs (H2N7; H5N1) were able to be phylogenetically examined. These analyses showed that viruses from Iceland shorebirds were primarily derived from Eurasian lineage viruses, yet the H2 hemagglutinin gene segment was from a North American lineage previously detected in a gull from Iceland the previous year. The H5N1 virus was determined to be low pathogenic, however the PB2 gene was closely related to the PB2 from highly pathogenic H5N1 isolates from China. Multiple lines of evidence suggest that the turnstones were infected with at least one of these AIV while in Iceland and confirm Iceland as an important location where AIV from different continents interact and reassort, creating new virus genomes. Mounting data warrant continued surveillance for AIV in wild birds in the North Atlantic, including Canada, Greenland, and the northeast USA to determine the risks of new AI viruses and their intercontinental movement in this region.

NK Cell Autoreactivity and Autoimmune Diseases

Increasing evidences have pointed out the relevance of natural killer (NK) cells in organ-specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands up-regulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILCs), comprising the classical CD56+ NK cells, have a role in maintaining or alternating tissue homeostasis secreting protective and/or pro-inflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular-matrix components, and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity.

Serum virus neutralization assay for detection and quantitation of serum-neutralizing antibodies to influenza A virus in swine.

The serum virus neutralization (SVN) assay is a serological test to detect the presence and magnitude of functional systemic antibodies that prevent infectivity of a virus. The SVN assay is a highly sensitive and specific test that may be applied to influenza A viruses in swine to measure the titer of neutralizing antibodies post-infection or after vaccination. Conventional SVN methods performed in vitro are based on inhibition of virus infectivity in cell culture in the presence of neutralizing antibodies. Titer determination may be based on the presence or the absence of cytopathic effect or the evidence of viral infection using an immunoreactive technique. The SVN assay is relatively inexpensive using standard laboratory equipment although it requires cell culture, more time and labor, and technical skill to conduct the assay compared to other serological methods. The SVN test is useful to evaluate the level of serological cross-reactivity between vaccine antisera and variant influenza viruses that may correlate with cross-protection in the host.

Bacterial Complications of Respiratory Tract Viral Illness: A Comprehensive Evaluation

Background. Respiratory tract infection is one of the most common reasons for hospitalization among adults, and recent evidence suggests that many of these illnesses are associated with viruses. Although bacterial infection is known to complicate viral infections, the frequency and impact of mixed viral-bacterial infections has not been well studied. Methods. Adults hospitalized with respiratory illness during 3 winters underwent comprehensive viral and bacterial testing. This assessment was augmented by measuring the serum level of procalcitonin (PCT) as a marker of bacterial infection. Mixed viral-bacterial infection was defined as a positive viral test result plus a positive bacterial assay result or a serum PCT level of ≥ 0.25 ng/mL on admission or day 2 of hospitalization. Results. Of 842 hospitalizations (771 patients) evaluated, 348 (41%) had evidence of viral infection. A total of 212 hospitalizations (61%) involved patients with viral infection alone. Of the remaining 136 hospitalizations (39%) involving viral infection, results of bacterial tests were positive in 64 (18%), and PCT analysis identified bacterial infection in an additional 72 (21%). Subjects hospitalized with mixed viral-bacterial infections were older and more commonly received a diagnosis of pneumonia. Over 90% of hospitalizations in both groups involved subjects who received antibiotics. Notably, 4 of 10 deaths among subjects hospitalized with viral infection alone were secondary to complications of Clostridium difficile colitis. Conclusions. Bacterial coinfection is associated with approximately 40% of viral respiratory tract infections requiring hospitalization. Patients with positive results of viral tests should be carefully evaluated for concomitant bacterial infection. Early empirical antibiotic therapy for patients with an unstable condition is appropriate but is not without risk.

Long double stranded RNA is present in scrapie infected cells and tissues

Despite decades of research efforts, the nature of the infectious agent causing scrapie and other Transmissible Spongiform Encephalopathies (TSE) remains an enigma. The protein-only prion hypothesis posits that an abnormal conformer of a host protein is the infectious agent. Virus and virino theories include host-independent nucleic acids in the genome of the infectious agent, in addition to the protein component (a host protein in the case of virino, and a viral protein in the case of a virus). Viral or sub-viral nucleic acids have long been sought in scrapie to explain the existence of multiple agent strains. Despite a plethora of different approaches to the search, no scrapie-specific nucleic acid sequences have been found in infected cells or tissues. Most viruses induce synthesis of long double stranded RNA (dsRNA) during their replication in cells, and thus the presence of long dsRNA would be an indication of viral infection in cells. J2 monoclonal antibody against long dsRNA is a useful tool for easy screening of cells and tissues for the presence of suspected viral infection; however, this antibody has not previously been used for testing of scrapie infected tissues. Here, we present evidence for long dsRNA in scrapie infected cells and tissues. Such dsRNA is also found in scrapie free tissue culture cells. We believe this may be the first evidence of viral infection in scrapie susceptible and infected cells.

Long double stranded RNA is present in scrapie infected cells and tissues

Despite decades of research efforts, the nature of the infectious agent causing scrapie and other Transmissible Spongiform Encephalopathies (TSE) remains an enigma. The protein-only prion hypothesis posits that an abnormal conformer of a host protein is the infectious agent. Virus and virino theories include host-independent nucleic acids in the genome of the infectious agent, in addition to the protein component (a host protein in the case of virino, and a viral protein in the case of a virus). Viral or sub-viral nucleic acids have long been sought in scrapie to explain the existence of multiple agent strains. Despite a plethora of different approaches to the search, no scrapie-specific nucleic acid sequences have been found in infected cells or tissues. Most viruses induce synthesis of long double stranded RNA (dsRNA) during their replication in cells, and thus the presence of long dsRNA would be an indication of viral infection in cells. J2 monoclonal antibody against long dsRNA is a useful tool for easy screening of cells and tissues for the presence of suspected viral infection; however, this antibody has not previously been used for testing of scrapie infected tissues. Here, we present evidence for long dsRNA in scrapie infected cells and tissues. Such dsRNA is also found in scrapie free tissue culture cells. We believe this may be the first evidence of viral infection in scrapie susceptible and infected cells.

Long double stranded RNA is present in scrapie infected cells and tissues

Despite decades of research efforts, the nature of the infectious agent causing scrapie and other Transmissible Spongiform Encephalopathies (TSE) remains an enigma. The protein-only prion hypothesis posits that an abnormal conformer of a host protein is the infectious agent. Virus and virino theories include host-independent nucleic acids in the genome of the infectious agent, in addition to the protein component (a host protein in the case of virino, and a viral protein in the case of a virus).Viral or sub-viral nucleic acids have long been sought in scrapie to explain the existence of multiple agent strains. Despite a plethora of different approaches to the search, no scrapie-specific nucleic acid sequences have been found in infected cells or tissues.Most viruses induce synthesis of long double stranded RNA (dsRNA) during their replication in cells, and thus the presence of long dsRNA would be an indication of viral infection in cells. J2 monoclonal antibody against long dsRNA is a useful tool for easy screening of cells and tissues for the presence of suspected viral infection; however, this antibody has not previously been used for testing of scrapie infected tissues.Here, we present evidence for long dsRNA in scrapie infected cells and tissues. Such dsRNA is also found in scrapie free tissue culture cells. We believe this may be the first evidence of viral infection in scrapie susceptible and infected cells.

In vitro assessment of the inflammatory breast cancer cell line SUM 149: Discovery of two single nucleotide polymorphisms in the RNase L gene.

196 Background: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer, accounting for 5% of breast cancers diagnosed annually in the United States. Understanding the distinct biology of IBC could help provide novel treatment targets. We sought to evaluate whether or not the IBC cell lines SUM 149 and SUM 190 demonstrated evidence of viral infection. Methods: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We also performed proliferation assays; developed dose response curves to assess the treatment effect of interferon-alpha (IFN-a); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated but not definitively associated with IBC,) in the DNA and RNA of SUM 149 cells. Results: According to our allelic discrimination SNP assay, 2/2 IBC cell lines were homozygous for the 462 and 541 variants, whereas 0/10 non-IBC cell lines were homozygous positive for the 462 variant (p = 0.015) and 2/10 non-IBC cell lines contained homozygous alleles for the 541 variant (p = 0.52). We also found a dose and time-dependent decrease in the proliferation of SUM 149 IBC cells treated with IFN-a. In contrast, non-IBC cell lines did not show a dose-response decrease in cell proliferation. Our reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis for the env/LTR and late LTR sequences of the putative HMTV revealed no evidence of the putative viral genome. Conclusions: We discovered 2 SNPs, in the 462 and 541 variants of the RNase L gene, that were homozygously mutated in IBC cell lines but the 462 variant was absent in non-IBC lines. Our discovery of these mutated SNPs present in IBC cell lines suggests a possible genetic risk factor for IBC. In our study, the IBC cell line SUM 149 demonstrated a direct and specific response to treatment with IFN-a, an antiviral agent. We noted no evidence of HMTV infection in that cell line. Further studies of the prevalence and significance of the RNase L 462 and 541 variants in human IBC tissue specimens are warranted to validate our in vitro findings.

A phase II feasibility study of sorafenib and gemcitabine combination therapy in advanced hepatocellular carcinoma.

298 Background: Sorafenib is considered standard of care in advanced hepatocellular carcinoma (HCC) giving survival benefit of around 4 months. Its combination with gemcitabine, a pyrimidine analogue with limited friendly hepatic profile, may improve results. The primary objective of this study was to evaluate the efficacy and safety of sorafenib and gemcitabine combination in advanced HCC. Methods: 30 patients of advanced HCC were enrolled in this non-randomized, open-label treatment protocol. Sorafenib 400 mg orally twice daily with gemcitabine 1,000mg/m2 intravenous on day 1 and 8 of a 4 week cycle for 4 months. Inclusion criteria: Child class A and B, adequate liver, marrow and renal functions, at least one uni-dimensional measureable lesion, Exclusion criteria: uncontrolled hypertension, serious infections, brain metastasis, bleeding diathesis, pregnant or lactating. National Cancer Institute criteria for adverse events (NCI CTCAE) Version 3.0, and Response evaluation criteria for solid tumors (RECIST) was used for assessment. Results: 30 patients: 23 male and 7 female. 24 (80%) Child class A and 6 (20%) class B. All had chronic liver disease. 22 (73.3%) had significantly high alfa-fetoprotein levels (≥ 500). 20 (66.7%) positive for hepatitis C, 4 (13.3%) for hepatitis B. 6 (20%) had no evidence of viral infection. 19 (63.3%) had multifocal lesions and 11 (36.7%) unifocal. 18 (60%) completing 4 cycles of treatment were assessed for response. 2 partial responses (PR) and 8 stable disease (SD) were seen. No complete response (CR) was observed. 8 patients had progressive disease, 4 progressing on interim assessment were taken off protocol. Toxicity: primarily hematological. Gemcitabine related thrombocytopenia being the most common (40%) requiring frequent dose modifications and delays. Sorafenib specific, hand foot skin reaction and anorexia were next most frequent. Conclusions: Sorafenib and gemcitabine combination is not feasible in advanced HCC due to its hematological toxicity especially thrombocytopenia, requiring frequent dose reductions and delays. No significant financial relationships to disclose.

Mycophenolate mofetil-induced agranulocytosis in a renal transplant recipient

A 27-year-old woman underwent living kidney transplantation from her mother. She received basiliximab, tacrolimus, mycophenolate mofetil (MMF), and a corticosteroid. Before transplantation, her complete blood count and white cell differential were normal. On about the 70th postoperative day (POD 70), her white blood cell (WBC) count began to decrease. On POD 113, her WBC count was 2800/μL. There was no evidence of viral infection, other systemic infection or malignancy. Drug-induced neutropenia, especially MMF-induced neutropenia, was suspected, and the dosage of MMF was reduced. However, the neutrophil count fell to 0/μL within 2 weeks. We further reduced the dosage of MMF and administered granulocyte-colony stimulating factor (G-CSF), which only temporarily increased the neutrophil count. Then, MMF was discontinued and switched to azathioprine, resulting in recovery of neutrophil count without subsequent rejection. MMF-induced neutropenia frequently occurs and should be monitored not only by WBC count but also by white cell differential count, since early discontinuation is the key to successful resolution of neutropenia. Switching from MMF to azathioprine or administration of G-CSF with or without MMF discontinuation might be options for treatment to avoid subsequent rejection.

Antibodies to Pathogenic Livestock Viruses in a Wild Vicuñe;a (Vicugna vicugna) Population in the Argentinean Andean Altiplano

Serum samples from 128 wild vicuñas (Vicugna vicugna) were tested for antibodies (Ab) to rotavirus (RV), bovine parainfluenza virus 3 (BPIV-3), bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus (BVDV-1), foot-and-mouth disease virus (FMDV), bluetongue virus (BTV), equine herpesvirus-1 (EHV-1), and influenza A virus equine (EIV). Samples were collected in Cieneguillas Province of Jujuy, in northern Argentina. Feces from 44 vicuñas were also collected to investigate RV shedding. Llamas (Lama glama) and domestic cattle (Bos taurus) from the area studied also were tested for antibodies to these viruses. Antibodies against RV (100%) and BPIV-3 (37%) were detected in the vicuñas sampled. No RV antigen was detected in any of the fecal samples tested. One vicuña was positive for Ab to BHV-1 (0.8%) and another for BVDV-1 (0.8%). The Ab prevalences detected in llamas were: 100% (16/16) for RV, 47% (8/17) for BPIV-3, 17.6% (3/17) for BHV-1, and 5.9% (1/17) for BVDV-1. However, domestic cattle had high antibody prevalences for RV and BPIV-3, 100% (13/13) and 73% (11/15), respectively, but were negative for Ab to BHV-1 and BVDV. No antibodies against FMDV, BTV, EHV-1, or EIV were detected in wild vicuñas or domestic species. Because no data of viral circulation on wild vicuñas are available, this report represents the first evidence of viral infection in wild vicuñas from the Argentinean Andean Puna.

Is Koi Herpesvirus (KHV) Related to the Mass Mortality Occurring among Cultured Carp, Cyprinus carpio, in Korea?

Since 1998, a new viral disease with high mortality has been consistently recorded in Korea in cultured carp, Cyprinus carpio. In this study, we investigated an epizootic of the disease that caused high mortality rates in carp obtained from 11 farms in Korea between 1999 and 2007. Assessment of koi herpesvirus (KHV) levels in diseased carp was carried out to determine if this virus was the etiologic agent of disease in this instance. High mortality rates in carp were recorded mainly in the spring and autumn at water temperatures between <TEX>$19^{\circ}C$</TEX> and <TEX>$24^{\circ}C$</TEX>. Diseased fish typically showed surface discoloration, with a thick opaque mucus covering the body and gills. Protozoan parasites and bacteria were recovered from 7/29 (24%) and 2/26 (8%) of fish, respectively. Evidence of viral infection was marked; cytopathic effects (CPEs), characterized by cell rounding and an extended cytoplasm in fathead minnow (FHM) cells, were detected in 40/41 fish (98%). A high mortality rate (80%) resulted when supernatants of cell cultures showing CPEs were applied to previously healthy fish. KHV was detected by polymerase chain reaction in 6/41 fish (15%), but was not detected in supernatants obtained from cell cultures showing CPEs. These results suggest that KHV may not be the etiologic agent of the high mortality occurring among cultured carp in Korea; therefore, some other-as yet unidentified-infective agent must be responsible.

Respiratory Viral Infections in Children With Leukemia

Respiratory viruses occur frequently in the community and are a common cause of fever in children. Data on respiratory viral infections in children with cancer are limited. A long-term, prospective, multicenter study was carried out in Finland searching for respiratory viruses in febrile children with leukemia. For this purpose, 138 febrile episodes in 51 children with leukemia were analyzed. Twelve types of respiratory viruses were searched for by viral culture, antigen detection, and polymerase chain reaction tests. Evidence of a respiratory viral infection was found in 61 of 138 febrile episodes (44%), accounting for an incidence of 0.8 (range, 0-2.4) per person year at risk during the treatment of leukemia. The most common viruses detected were rhinovirus (22%), respiratory syncytial virus (11%), human bocavirus (5%), and influenza A virus (4%). Dual viral infections were detected in 12 cases (9%). Half of the children had respiratory symptoms with cough being the most common symptom. Two children developed pneumonia. The mean duration of fever was 2.6 (SD 1.7) days in children with respiratory viral infection and 2.1 (SD 1.3) days in children without evidence of viral infection (P = 0.44). Respiratory viruses are found commonly during febrile episodes in children with leukemia. The detection of viruses permits the use of available antiviral agents, may explain a poor response to antimicrobial agents, and minimizes the proportion of febrile episodes without possible etiologic agents in children with leukemia.

Fulminant Hepatic Failure as the Initial Manifestation of Small-Cell Lung Cancer: Report of 2 Cases

In this report, we describe two cases of small-cell lung cancer (SCLC) presenting with fulminant hepatic failure as the initial manifestation. Neither of the patients had a previous history of liver disease, evidence of viral infection, or exposure to hepatotoxins. Both presented with hepatomegaly and an increase in the serum LDH level. Although they had a history of smoking and respiratory symptoms such as dyspnea on exertion, their most striking initial symptoms were those of hepatic failure, which made it difficult to suspect the underlying primary lung cancer. In one case, contrast-enhanced CT of the abdomen revealed hypovascular nodules that were not visible on plain CT. After a rapidly deteriorating course, both patients died, 8 and 13 days after admission, respectively. Autopsy revealed diffuse infiltration of the hepatic sinusoids and extensive replacement of the liver parenchyma by metastatic small-cell carcinoma. We conclude that metastatic SCLC should be considered in the differential diagnosis in patients of advanced age with a smoking history presenting with rapidly progressive liver failure associated with hepatomegaly and elevation of the serum LDH.

Activity of the Anti-Orthopoxvirus Compound ST-246 against Vaccinia, Cowpox and Camelpox Viruses in Cell Monolayers and Organotypic Raft Cultures

The potential use of variola virus as a biological weapon has renewed efforts in the development of antiviral agents against orthopoxviruses. ST-246 [4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-di oxo-4,6-ethenocycloprop [f]isoindol-2(1 H)-yl)-benzamide] is an anti-orthopoxvirus compound active against several orthopoxviruses including vaccinia virus (VV), cowpox virus (CPV), camelpox virus (CMLV), ectromelia virus (ECTV) and variola virus in cell culture. The compound has been shown to inhibit the release of extracellular virus by targeting the F13L W protein and to protect mice from W, CPV and ECTV orthopoxvirus-induced disease. The antiviral activity of ST-246 was assessed against extracellular and intracellular W, CPV and CMLV production in human embryonic lung (HEL) fibroblasts and primary human keratinocyte (PHK) cell monolayers, as well as in three-dimensional raft cultures. ST-246 inhibited preferentially the production of extracellular virus compared with intracellular virus production in HEL and PHK cells (for W) and in PHK cells (for CMLV). In organotypic epithelial raft cultures, ST-246 at 20 microg/ml inhibited extracellular W and CMLV production by 6 logs, whereas intracellular virus yield was reduced by 2 logs. In the case of CPV, both extracellular and intracellular virus production were completely inhibited by ST-246 at 20 microg/ml. Histological sections of the infected rafts, treated with increasing amounts of drug, confirmed the antiviral activity of ST-246: the epithelium was protected and there was no evidence of viral infection. Electron microscopic examination confirmed the absence of intracellular enveloped virus forms in W-, CPV- and CMLV-infected cells treated with 10 microg/ml of ST-246. These data indicate that ST-246 is a potent anti-orthopoxvirus compound; the mode of inhibition is dependent on the virus and cell type.

Emergence of panniculitis and haemophagocytic syndrome in a patient with chronic systemic lupus erythematosus

Panniculitis rarely occurs in the course of systemic lupus erythematosus (SLE). When it occurs, it is thought to be mainly lupus erythematosus panniculitis (LEP). Here we describe a 32-year old Japanese woman with chronic SLE, who simultaneously presented facial lymphocytic lobular panniculitis and pancytopenia due to haemophagocytic syndrome. She showed several auto-antibodies against trilineage haematopoetic cells, an anti-cardiolipin antibody, and no evidence of viral infection, indicating that her haemophagocytic syndrome might be autoimmune-associated haemophagocytic syndrome. The panniculitis and haemophagocytic syndrome presented simultaneously, and these manifestations were dramatically improved with corticosteroid therapy; therefore, the lymphocytic lobular panniculitis could be linked to autoimmune-associated haemophagocytic syndrome in this case.

In situ detection of SOCS and cytokine expression in the uterine cervix from HIV/HPV coinfected women

The purpose of this study was to look for associations between a newly described class of suppressors of cytokine signaling (SSI/SOCS) and cytokine expression in the uterine cervix from HIV/HPV coinfected women. We examined the pro-inflammatory cytokines TNF-α and IL-6 since their expressions are linked and responsible for many aspects of both localized and systemic inflammatory responses. Further, expression of SSI/SOCS has been implicated in the negative feedback regulation of cytokine receptor signaling. PCR-amplified HIV-1 cDNA was noted mainly in the stroma, showing a perivascular distribution, and most of the infected cells colabeled with the macrophage marker CD68. The distribution of IL-6 and TNF-α was in the same area to HIV-1 and much greater than normal cervices from women with no evidence of viral infection. SOCS/SSI-1 and -3 mRNA positive cells in the uterine cervix were commonly detected in these noninfected cervical tissues; however, very few cells that contained SOCS were evident in areas where HIV-1, TNF-α, and IL-6 expressing cells were found. This suggests that viral-related suppression of SOCS/SSI-1-3 expression may be a factor in the marked local enhancement of TNF-α and IL-6 production which, in turn, may help facilitate viral spread; however, further studies should be done in order to elucidate the exact mechanisms of SOCS in the cervix.

Evidence that spontaneous reactivation of herpes virus does not occur in mice

BackgroundSome species, including humans and rabbits, exhibit periodic viral reactivation and shed infectious virus at the infected end organ. Mice may be an exception, because spontaneous shedding of infectious virus rarely, if ever, occurs. However, spontaneous molecular reactivation, i.e., the expression of a few viral genes and the synthesis of the viral glycoproteins coded for by these genes, has been reported. This finding has prompted the assumption that molecular reactivation is an indicator of reactivation and the production of infectious virus. The goal of this study was to differentiate between viral gene expression during latency and the episodic production of infectious virus in mice.ResultsViral reactivation and infection were not seen in herpes simplex virus type 1 (HSV-1) latent ganglion graft recipient BALB/c scid or immunocompetent BALB/c mice, which survived the 65-day observation period with no evidence of viral infection although the immunocompetent mice developed cellular and humoral immunity to HSV-1. In contrast, BALB/c scid recipients of ganglia containing reactivating virus invariably developed a local and, subsequently, systemic viral infection and died within 14 days. Immunocompetent BALB/c mice that received ganglion grafts containing reactivating virus survived the infection and became immune to the virus. Trigeminal ganglia removed from scid and immunocompetent recipient graft sites 5, 14, and 28 days after transplantation contained latent virus and viable neurons.ConclusionThe results suggest that, within the limits of detection of the experiments, spontaneous episodic production of immunogenic viral antigens but not of infectious virus occurs in mouse neural ganglia during latency.

Monitoring for Presence of Potentially Xenotic Viruses in Recipients of Pig Islet Xenotransplantation

This study represents a long-term follow-up of human patients receiving pig islet xenotransplantation. Eighteen patients had been monitored for up to 9 years for potentially xenotic pig viruses: pig endogenous retrovirus, pig cytomegalovirus, pig lymphotropic herpesvirus, and pig circovirus type 2. No evidence of viral infection was found.