Amy S. Arrington

Simian virus 40 in human cancers

BACKGROUND Many studies have reported the presence of simian virus 40 (SV40) deoxyribonucleic acid (DNA) or protein in human brain tumors and bone cancers, malignant mesothelioma, and non-Hodgkins lymphoma. However, the small samples and lack of control groups in some reports have made it difficult to assess their reliability. METHODS Studies were included in this analysis if they met the following criteria: original studies of patients with primary brain tumors and bone cancers, malignant mesothelioma, or non-Hodgkins lymphoma; the investigation of SV40 was performed on primary cancer specimens; the analysis included a control group; and the same technique was used for cases and controls. Included reports were published from 1975 to 2002. RESULTS Thirteen studies fulfilled the criteria for the investigation of primary brain cancers (661 tumors and 482 control samples). Specimens from patients with brain tumors were almost four times more likely to have evidence of SV40 infection than were those from controls (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 2.6 to 5.8). The association was even stronger for mesothelioma (OR = 17; 95% CI: 10 to 28; based on 15 studies with 528 mesothelioma samples and 468 control samples) and for bone cancer (OR = 25; 95% CI: 6.8 to 88; based on four studies with 303 cancers and 121 control samples). SV40 DNA was also more frequent in samples from patients with non-Hodgkins lymphoma (OR = 5.4; 95% CI: 3.1 to 9.3; based on three studies with 301 cases and 578 control samples) than from controls. CONCLUSION These results establish that SV40 is associated significantly with brain tumors, bone cancers, malignant mesothelioma, and non-Hodgkins lymphoma. Studies are needed to assess current prevalence of SV40 infections.

Evidence of SV40 infections in hospitalized children

Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.

SV40-positive brain tumor in scientist with risk of laboratory exposure to the virus.

Simian virus 40 (SV40) is a DNA tumor virus known to induce cancers in laboratory animals. There are numerous reports of the detection of SV40 DNA and/or proteins in human malignancies of the same types as those induced by SV40 in animals, including brain cancers. However, known exposure to the virus has not yet been linked directly to cancer development in a specific individual. Here we describe the detection of SV40 sequences in the meningioma of a laboratory researcher who had a probable direct exposure to SV40 and subsequently developed a tumor positive for viral DNA sequences indistinguishable from those of the laboratory source. This case suggests a link between viral exposure and tumor development.

Viral regulatory region effects on vertical transmission of polyomavirus SV40 in hamsters

Viral strain differences influence the oncogenic potential of polyomavirus simian virus 40 (SV40). We hypothesized that viral strain differences might also affect vertical transmission of SV40 in susceptible hosts. Pregnant Syrian golden hamsters were inoculated intraperitoneally with 10(7) plaque-forming units of SV40 and offspring were sacrificed post-delivery (1-21 days, 6 months). Organ extracts were analyzed for SV40 DNA by polymerase chain reaction assay. Transmission of SV40 from mother to offspring was detected in over half of litters. Most placentas were virus-positive. Mothers inoculated with SV40 strains containing complex regulatory regions transmitted virus more frequently than those infected with simple enhancer viruses (p<0.001). Virus was detected more often in progeny brain than in spleen (p<0.05). Several progeny were virus-positive at 6 months of age, suggesting viral persistence. Maternal animals retained virus in several tissues through day 21 and developed T-antigen antibodies. These results indicate that SV40 replicates in hamsters, vertical transmission of SV40 can occur, and the viral regulatory region influences transmission.

Biocontainment Principles for Pediatric Patients

The need for medical communities to prepare for highly hazardous communicable disease outbreaks was perhaps best exemplified in the 2014–2016 Ebola virus outbreak. To date, most efforts of preparedness have focused on adult medical providers, though it is critical that pediatric institutions achieve the same level of preparedness for children who may present with these illnesses. Care of pediatric patients exposed and/or infected with these unique pathogens requires advanced planning and training in order to offer the highest level of care while at the same time being able to ensure the safety of both the hospital staff and the community. In this chapter, we will discuss the basic principles of biocontainment and care in a unique pediatric setting and offer guidelines on how to navigate the identification, isolation, family-centered care, and clinical care of children with highly hazardous communicable diseases.

Polyomaviruses in Kidney Transplant Recipients

In their discussion the authors reported that a retrospective evaluation of the samples from 32 of the 54 patients showed the presence of BKV in all samples, with evidence of concurrent JCV reactivation in eight patients. However, no information was provided regarding the methodology of that investigation, and it appears that the specimens were not evaluated for the presence of polyomavirus SV40. This is important as the homology between the two human polyomaviruses (JCV and BKV) and SV40 is approximately 70%, and recent reports indicate that SV40 can cause infections in kidney transplant recipients.