RESUMO
Targeted gene therapy using recombinant adeno-associated virus (rAAV) vectors is a potential therapeutic strategy for treating cancer, and tissue-specific promoters may help with tissue targeting. Medullary thyroid carcinoma (MTC) is a disease of the calcitonin secreting thyroid C cells, and calcitonin is highly expressed in MTC tumors compared to other cells. To target MTC cells, we evaluated an rAAV serotype 2 vector (rAAV2-pM+104-GFP) containing a modified calcitonin/calcitonin gene related peptide promoter (pM+104) and a green fluorescent protein (GFP) reporter gene. In vitro transduction experiments comparing the MTC TT cell line with non-MTC cell lines demonstrated that rAAV2-pM+104-GFP infection yielded significantly (p < 0.05) higher GFP expression in TT cells than in non-MTC cell lines (HEK293 and HeLa), and significantly higher expression than in TT cells infected with the positive control rAAV2-pCBA-GFP vector. The rAAV2-pCBA-GFP control vector included a well-characterized, ubiquitously expresses control promoter, the chicken beta actin promoter with a cytomegalovirus enhancer (pCBA). In vivo experiments using a TT cell xenograft tumor mouse model showed that tumors directly injected with 2 x 1010 vg of rAAV2-pM+104-GFP vector resulted in GFP expression detected in 21.7% of cells, 48 hours after the injection. Furthermore, GFP expression was significantly higher for rAAV-pM+104-GFP treatments with a longer vector treatment duration and higher vector dose, with up to 52.6% (q < 0.05) GFP cells detected 72 hours after injecting 1x 1011 vg/tumor. These data show that we have developed an rAAV vector with improved selectivity for MTC.
Assuntos
Calcitonina/genética , Carcinoma Neuroendócrino/terapia , Dependovirus/genética , Vetores Genéticos/metabolismo , Sequências Reguladoras de Ácido Nucleico/genética , Neoplasias da Glândula Tireoide/terapia , Animais , Peptídeo Relacionado com Gene de Calcitonina/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Células HeLa , Humanos , Luciferases/metabolismo , Masculino , Camundongos SCID , Regiões Promotoras Genéticas , Transgenes , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: Several aspects of medical training may contribute to the ultimate goal of producing excellent physicians whose patients will have the best possible outcomes. However, the relative importance of education, evaluation and feedback, duty hours, practice structure, and program culture in achieving this goal is unclear. This study assessed associations among in-training exam performance, Accreditation Council for Graduate Medical Education (ACGME) Resident Survey responses, and American Board of Medical Specialties (ABMS) national board exam performance. METHODS: Residency training programs at a university teaching hospital were classified as having 5-year first-time ABMS pass rates above (n=12) or below (n=3) the national average for their specialty. These groups were compared by ACGME Resident Survey data and in-training exam performance. RESULTS: Surveys were collected from 484/543 eligible residents (89%), including 177 surveys from programs with below-average board pass rates and 307 surveys from programs with aboveaverage board pass rates. In-training exam performance was similar between groups. Aboveaverage programs had stronger agreement with statements that their culture reinforced patient safety (4.72 vs. 4.30, p=0.006) and that information was not lost during transitions of care (4.14 vs. 3.63, p=0.001). Although the occurrence of interprofessional teamwork was similar between groups, above-average programs had stronger agreement with the statement that interprofessional teamwork was effective (4.60 vs. 4.17, p=0.003). CONCLUSION: Residency programs emphasizing patient safety and effective interprofessional teamwork had above-average first-time national board pass rates.
Assuntos
Educação de Pós-Graduação em Medicina , Internato e Residência , Equipe de Assistência ao Paciente , Segurança do Paciente , Acreditação , Educação de Pós-Graduação em Medicina/normas , Avaliação Educacional , Retroalimentação , Humanos , Tolerância ao Trabalho ProgramadoRESUMO
Parvoviruses are some of the smallest DNA viruses known to infect a wide range of animal species and humans. Though not all parvoviruses are pathogenic, some can cause disease ranging from asymptomatic to benign to life-threatening. Recently, there has been an interest in the possible role of parvoviruses in thyroid disease in general. The objectives of this review are to cite and appraise the available evidence on the role of parvoviruses in thyroid cancer in particular. Little to no evidence is available directly linking animal parvoviruses and thyroid cancer, but there is a growing literature on the human erythrovirus B19 (EVB19) and its association with thyroid cancer. Of particular interest is the persistence and expression of EVB19 DNA, RNA, and protein in a wide variety of thyroid tissues. While a causative role of EVB19 in the pathogenesis of thyroid cancer cannot be supported at this time, an indirect role is hypothesized and discussed but with the recognition that the data are limited. Further studies are clearly warranted to determine the exact, if any, role of this human pathogen in thyroid cancer.
Assuntos
Infecções por Parvoviridae/complicações , Neoplasias da Glândula Tireoide/virologia , Animais , Humanos , ParvovirusRESUMO
Parvovirus B19 (B19V) is a small non-enveloped DNA virus of the Parvoviridae family. It is an obligate human pathogen that preferentially replicates in erythroid progenitor cells. B19V is the causative agent of multiple erythroid-related diseases due to replication-induced cytotoxicity. Despite its strong erythroid tropism and related acute disease association, B19V has been determined to persist in many other non-erythroid tissues. This review summarizes and appraises what is known about concomitant B19V DNA persistence and non-acute viral gene expression in various, particularly non-erythroid, tissue types. The methods utilized for B19V detection are described, focusing on the discrepancies in outcomes among the employed assays. The studies where investigations focused on the impact of persistent B19V expression on cellular signaling pathways are also summarized. These studies demonstrate the expanse of the types of cells capable of in vivo B19V expression as well as the possible effect of persistent viral infection on the cellular microenvironment. Overall, these reports indicate that B19V commonly persists in a wide range of both erythroid and non-erythroid tissues, and that low-level viral gene expression can be detected in some persistently infected cells. B19V capsid RNA or proteins have been reported in bone marrow, colon, heart, liver, lymphoid, synovial, testicular, and thyroid tissues. In a sub-set of these cases, B19V capsid mRNA or proteins have been associated with increased inflammatory-related gene expression. The development of standard protocols to assay for B19V infection and expression in the context of non-erythroid, non-acute disease is warranted, and with further targeted studies, may begin to elucidate the impact of persistent B19V infection in vivo. These studies may determine the most conducive cellular environment for persistent gene expression and possible impact on disease pathogenesis.
Assuntos
Infecções por Parvoviridae/imunologia , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/fisiologia , Progressão da Doença , Células Precursoras Eritroides/imunologia , Células Precursoras Eritroides/virologia , Humanos , Especificidade de Órgãos , Infecções por Parvoviridae/patologia , Parvovirus B19 Humano/genética , Replicação ViralRESUMO
Ovarian teratomas represent the most common neoplasm derived from germ cells and can contain mature ectodermal, mesodermal, and endodermal tissues. In rare cases, these teratomas can be composed predominantly or solely of thyroid tissue. These thyroid cells often function similarly to normal thyroid tissues. This laboratory and others have previously shown that parvovirus B19 (B19V) persists in primary and metastatic thyroid tissues. No reports exist on possible B19V persistence in thyroid tissues that may arise de novo outside the thyroid gland proper. In this case report, the detection of B19V (genotype 1) in the thyroid epithelial cells of a mature teratoma is reported. Nested PCR and immunohistochemistry were used to detect viral nucleic acids and proteins, respectively. Viral genomes were amplified in lesion DNA, confirming persistence of B19V. Positive immunohistochemical staining was seen for B19V capsid proteins in the thyroid epithelial cells within the mature teratoma, but not in surrounding ovarian tissue or in the non-thyroidal elements of the mature teratoma. These results demonstrate for the first time that thyroid epithelial cells, derived from non-thyroid tissue, are capable of supporting B19V infection and persistence.
Assuntos
Neoplasias Ovarianas/patologia , Parvovirus B19 Humano/isolamento & purificação , Teratoma/patologia , Glândula Tireoide/patologia , Proteínas do Capsídeo/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/virologia , Parvovirus B19 Humano/metabolismo , Teratoma/virologia , Glândula Tireoide/virologiaRESUMO
Human erythrovirus B19 (EVB19) is a small, pathogenic DNA virus that has been associated with a wide range of illnesses. The primary site of replication is in bone marrow-derived erythroid progenitor cells, but EVB19 DNA has been detected in a wide range of organs. Recently, studies have linked EVB19 to thyroid cancers and other thyroid diseases. Previous studies from multiple laboratories have detected EVB19 capsid proteins in Graves' disease, Hashimoto's thyroiditis, and thyroid cancer tissues. Data on viral gene expression and mechanism of infection in the thyroid are lacking. To investigate EVB19 infection and persistence in the thyroid, previously archived adult and pediatric tissue sections were examined for EVB19 DNA, RNA, and capsid proteins, as well as EVB19 receptor P-antigen and co-receptor α5ß1 integrin. EVB19 DNA and protein were detected in a majority of tissues examined (87% and 68%, respectively). Detection was similar in adult and pediatric samples. Quantification of viral genomes revealed no significant difference in the amount of viral DNA in benign, cancerous, or metastatic thyroid tissues. EVB19 capsid RNA was detected in 67% of the tissues examined, confirming at least low-level viral gene expression. Immunohistochemical staining for P-antigen and α5ß1 detected the receptor and co-receptor most frequently on normal thyroid epithelial cells. EVB19 capsid staining could be detected in tumors lacking viral receptors. These results suggest that normal thyroid epithelial cells are the initial target for EVB19 infection in the thyroid and allow for continued persistence in both normal and cancerous thyroid tissues.
Assuntos
Adenoma/virologia , Carcinoma Papilar/virologia , Erythrovirus/genética , Infecções por Parvoviridae/virologia , Glândula Tireoide/virologia , Neoplasias da Glândula Tireoide/virologia , Adenoma/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas do Capsídeo/metabolismo , Carcinoma Papilar/metabolismo , Carcinoma Papilar/secundário , Criança , DNA Viral/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Parvoviridae/metabolismo , Infecções por Parvoviridae/patologia , RNA Viral/genética , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Adulto JovemRESUMO
Erythrovirus B19 (B19V) is a member of the family Parvoviridae. Infection with B19V has been linked to a variety of diseases including erythroid, thyroid, neurological and autoimmune diseases. Here we show that infection of primary CD36+ cells with B19V coincides with downregulation of thyroid, retinoid, and estrogen hormone receptors. In addition we show changes in expression of a variety of related downstream signaling genes participating in cancer and cardiac-related diseases in B19V-infected erythroid primary cells.
Assuntos
Interações Hospedeiro-Patógeno , Células Progenitoras Mieloides/virologia , Parvovirus B19 Humano/fisiologia , Receptores de Estrogênio/biossíntese , Receptores do Ácido Retinoico/biossíntese , Receptores dos Hormônios Tireóideos/biossíntese , Replicação Viral , Antígenos CD36/análise , Células Cultivadas , Regulação para Baixo , Humanos , Células Progenitoras Mieloides/química , Transdução de SinaisRESUMO
OBJECTIVE: The purpose of this study was to examine trends in the Psychiatry Resident-In-Training Examination (PRITE®) scores at one institution from 2001 to 2010. The authors hypothesized that two factors, the 2003 implementation of the Accreditation Council for Graduate Medical Education (ACGME) duty-hour restrictions and the residency program's 2008 restructuring of its curriculum to a half-day per week of didactics, would lead to improved scores. METHOD: Residents in the general psychiatry program at the University of Florida College of Medicine from 2001 to 2010 were included in this study. To examine the effect of the 2003 ACGME duty-hours change, the authors compared test results from 2001-2002 and 2003-2010. To examine the effect of the 2008 didactic restructuring, they compared test results from 2001-2007 and 2008-2010. RESULTS: There were 288 PRITE test scores from 2001 to 2010. The authors did not find a statistical difference between test results before and after the 2003 implementation of ACGME duty-hour restrictions or between test results before and after the 2008 restructuring of residency didactics. CONCLUSION: The hypothesis was rejected. The results of the literature review propose that examination scores are affected by other elements of residency training.
Assuntos
Educação de Pós-Graduação em Medicina/normas , Avaliação Educacional/estatística & dados numéricos , Internato e Residência/normas , Psiquiatria/educação , Acreditação/normas , Acreditação/tendências , Currículo/tendências , Educação de Pós-Graduação em Medicina/tendências , Humanos , Internato e Residência/tendências , Admissão e Escalonamento de Pessoal/normas , Admissão e Escalonamento de Pessoal/tendências , Tolerância ao Trabalho Programado , Carga de Trabalho/normasRESUMO
BACKGROUND: Parvovirus B19 (B19V) is a common pathogenic virus infecting humans. Previous studies have shown evidence of B19V infection in patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma using ELISA and PCR on serum specimens. B19V nonstructural protein is known to alter the expression of cellular factors including interleukin-6 (IL-6), which can increase the risk for and worsen the prognosis of lymphomas. OBJECTIVE: The objective of this study was to detect B19V capsid protein and IL-6 expression in normal and malignant lymphoid tissue, as well as any correlation between the two. STUDY DESIGN: IHCs for B19V capsid protein, IL-6, and B19V co-receptors P-antigen and α5ß1 integrin were performed on a tissue array containing 70 duplicated pediatric and adult lymphoma tissues and 5 duplicated benign lymph node sections. Cases were identified as normal, B-cell NHL, diffuse large B-cell NHL, Hodgkin's lymphoma, extranodal NK/T cell lymphoma, anaplastic large cell lymphoma, or mantle cell lymphoma. IL-6 and B19V capsid staining were quantified using a positive pixel count algorithm, and P-antigen and α5ß1 staining using a membrane quantification algorithm. RESULTS: B19V capsid protein was detected in both benign and malignant lymphoid tissue. The Spearman rank correlation coefficient analysis was performed to determine the relationship between the level of positivity for B19V and IL-6 staining, yielding an overall correlation coefficient of 0.679 (p-value<0.0001). CONCLUSIONS: Our results show a moderate correlation between the levels of positive B19V and IL-6 staining by IHC, indicating a possible role for B19V in the pathogenesis of lymphomas.
Assuntos
Proteínas do Capsídeo/análise , Interleucina-6/análise , Tecido Linfoide/imunologia , Tecido Linfoide/virologia , Infecções por Parvoviridae/imunologia , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imuno-Histoquímica , Linfoma/imunologia , Linfoma/patologia , Linfoma/virologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To detect B19 capsid proteins, VP1 and VP2, in testicular tissues, both normal and tumor, using immunohistochemistry. METHODS: Samples of normal, fetal, and tumor testicular tissue (n = 31) and normal testicular DNA (n = 1) were tested for the presence of B19. Immunohistochemistry staining was used for the detection of viral capsid proteins VP1 and VP2. Polymerase chain reaction with 4 primer sets was used to test for the presence of B19 DNA in a normal testicular sample. RESULTS: B19 capsid protein VP1 and VP2 was detected by immunohistochemistry in 6 (85.7%) of 7 normal testicular samples and 17 (73.9%) of 23 tumor samples. The findings from a normal fetal testicular sample were equivocal. B19 DNA was detected in normal testicular DNA with 4 of the 4 primer sets used. CONCLUSION: In contrast to previous reports, B19 capsid proteins VP1 and VP2 have now been detected in both normal and tumor testicular tissue. The persistence of B19 in a diverse range of tissues, including the testes, requires more research into the molecular mechanisms by which B19 can enter these cells, as well as the possible etiologic roles in chronic diseases, including cancer.
Assuntos
Proteínas do Capsídeo/isolamento & purificação , Seminoma/metabolismo , Neoplasias Testiculares/metabolismo , Testículo/metabolismo , DNA Viral/metabolismo , Feto/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Reação em Cadeia da Polimerase , Testículo/embriologiaRESUMO
BACKGROUND: The human pathogenic parvovirus B19 (B19) has recently been detected in papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) tissues at a high frequency in two studies of a Chinese cohort. We wanted to extend these data to include another cohort and expand the thyroid tumor tissue types assessed. In particular, we were interested to find whether B19 also infects anaplastic thyroid carcinoma (ATC), one of the most aggressive human cancers. METHODS: Commercially available thyroid tumor tissue arrays were used to detect B19 capsid protein by immunohistochemistry in various types of thyroid tumors and disorders. The arrays were representative of the four main types of thyroid tumors, as well as other thyroid autoimmune disorders such as HT and Graves' disease, and adenomas, goiters, lymphomas, and normal thyroid tissue. In total, at least 12 different types of thyroid conditions as well as normal tissue were represented, many with multiple subjects. RESULTS: Twenty-one of the 24 (88%) PTC tumors, 3 of the 3 ATC/undifferentiated tumors, and 3 of the 3 HT tissue samples were positive for B19 capsid protein by immunohistochemistry. The localization of the protein differed based on pathological disease type, with a nuclear to cytoplasmic shift seen from unaffected to tumor tissue. CONCLUSIONS: We extend the data available on B19 detection in the thyroid to show a high correlation of virus in another cohort of PTC and HT at the protein level. We also show, for the first time, B19 infection of much more highly aggressive ATC/undifferentiated tumors. Nuclear to cytoplasmic shift in B19 protein in cancer tissue suggests a possible link between B19 and thyroid cancer pathogenesis/progression.
Assuntos
Doença de Hashimoto/virologia , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano , Proteínas do Capsídeo/análise , Carcinoma , Carcinoma Papilar/patologia , Doença de Hashimoto/patologia , Humanos , Imuno-Histoquímica , Câncer Papilífero da Tireoide , Carcinoma Anaplásico da Tireoide , Glândula Tireoide/virologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/virologia , Tireoidite Autoimune/patologiaRESUMO
We previously reported in a large cohort (N = 104) of post-mortem tissues the detection of both the non-pathogenic adeno-associated virus (AAV2) in approximately 13% and the pathogenic human parvovirus B19 (B19) in approximately 42% of human brains, particularly the dorsolateral prefrontal cortex. Multiple animal parvoviruses target the developing cerebellum (CBLM) resulting in hypoplasia and ataxia, but very little is known about the human parvoviruses and their ability to infect or cause disease in the CBLM. We have now confirmed in the above cohort the presence of AAV2 and B19 sequences in the CBLM. Our results show that approximately 27% and approximately 70% of human CBLM are positive by nested polymerase chain reaction for AAV2 and B19 sequences, respectively. We also document in a second cohort (N = 10) the presence of AAV2 (50%) and B19 (100%) sequences in the CBLM and correlate our results for B19 with studies from matched sera. Eighty percent (80%) of this cohort was positive for anti-B19 IgG, while none were IgM+, suggesting that most individuals had been previously infected with B19 but none acutely. To our knowledge, this study is the first to demonstrate that both AAV2 and B19 sequences are present at relatively high frequencies in the CBLM and are likely due to persistent rather than acute infection. Further studies will lead to insights into AAV2- and/or B19-CBLM interactions including mechanisms of infection, persistence, and possibly neuropathology, including cerebellar hypoplasia and ataxia.
Assuntos
Doenças Cerebelares/metabolismo , Doenças Cerebelares/virologia , Cerebelo/virologia , Dependovirus/genética , Parvovirus B19 Humano/genética , Idoso , Idoso de 80 Anos ou mais , Doenças Cerebelares/imunologia , Cerebelo/metabolismo , Distribuição de Qui-Quadrado , Estudos de Coortes , DNA Viral/genética , Dependovirus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Parvovirus B19 Humano/imunologia , Mudanças Depois da MorteRESUMO
We have documented that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects intracellular trafficking and transduction efficiency of recombinant adeno-associated virus 2 (AAV2) vectors. Specifically, inhibition of EGFR-PTK signaling leads to decreased ubiquitination of AAV2 capsid proteins, which in turn, facilitates viral nuclear transport by limiting proteasome-mediated degradation of AAV2 vectors. In the present studies, we observed that AAV capsids can indeed be phosphorylated at tyrosine residues by EGFR-PTK in in vitro phosphorylation assays and that phosphorylated AAV capsids retain their structural integrity. However, although phosphorylated AAV vectors enter cells as efficiently as their unphosphorylated counterparts, their transduction efficiency is significantly reduced. This reduction is not due to impaired viral second-strand DNA synthesis since transduction efficiency of both single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors is decreased by approximately 68% and approximately 74%, respectively. We also observed that intracellular trafficking of tyrosine-phosphorylated AAV vectors from cytoplasm to nucleus is significantly decreased, which results from ubiquitination of AAV capsids followed by proteasome-mediated degradation, although downstream consequences of capsid ubiquitination may also be affected by tyrosine-phosphorylation. These studies provide new insights into the role of tyrosine-phosphorylation of AAV capsids in various steps in the virus life cycle, which has implications in the optimal use of recombinant AAV vectors in human gene therapy.
Assuntos
Dependovirus/metabolismo , Receptores ErbB/metabolismo , Regulação Viral da Expressão Gênica , Vetores Genéticos/metabolismo , Transgenes/genética , Tirosina/metabolismo , Capsídeo/metabolismo , Caseína Quinase II/metabolismo , Núcleo Celular/metabolismo , Dependovirus/genética , Células HeLa , Humanos , Fosforilação , Transporte Proteico , Transdução Genética , UbiquitinaçãoRESUMO
Recombinant adeno-associated virus 2 (AAV2) vectors are in use in several Phase I/II clinical trials, but relatively large vector doses are needed to achieve therapeutic benefits. Large vector doses also trigger an immune response as a significant fraction of the vectors fails to traffic efficiently to the nucleus and is targeted for degradation by the host cell proteasome machinery. We have reported that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects transduction by AAV2 vectors by impairing nuclear transport of the vectors. We have also observed that EGFR-PTK can phosphorylate AAV2 capsids at tyrosine residues. Tyrosine-phosphorylated AAV2 vectors enter cells efficiently but fail to transduce effectively, in part because of ubiquitination of AAV capsids followed by proteasome-mediated degradation. We reasoned that mutations of the surface-exposed tyrosine residues might allow the vectors to evade phosphorylation and subsequent ubiquitination and, thus, prevent proteasome-mediated degradation. Here, we document that site-directed mutagenesis of surface-exposed tyrosine residues leads to production of vectors that transduce HeLa cells approximately 10-fold more efficiently in vitro and murine hepatocytes nearly 30-fold more efficiently in vivo at a log lower vector dose. Therapeutic levels of human Factor IX (F.IX) are also produced at an approximately 10-fold reduced vector dose. The increased transduction efficiency of tyrosine-mutant vectors is due to lack of capsid ubiquitination and improved intracellular trafficking to the nucleus. These studies have led to the development of AAV vectors that are capable of high-efficiency transduction at lower doses, which has important implications in their use in human gene therapy.
Assuntos
Dependovirus/genética , Vetores Genéticos , Mutação Puntual , Transdução Genética , Tirosina/genética , Animais , Capsídeo/metabolismo , Núcleo Celular/metabolismo , Terapia Genética , Células HeLa , Hepatócitos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , UbiquitinaçãoRESUMO
Although animal parvoviruses have long been recognized as causes of brain pathology in multiple animal models, especially during early development, human parvoviruses are rarely thought of as neurotropic or causes of neuropathology in humans. However, several recent case reports have suggested possible associations of parvovirus B19 (B19) infection with various neurological and neuropsychiatric symptoms. Adeno-associated virus 2 (AAV2) is related to B19 but has thus far not been shown to be associated with any human disease but is of clinical interest because of the recent use of recombinant AAV vectors in human gene therapy, including gene delivery to the brain. To date, there have been no large-scale studies of the propensity of wild-type human parvoviruses to infect the brain. The Stanley Medical Research Institute Brain Collection offered a unique opportunity to study a large sample (n = 104) of dorsolateral prefrontal cortex (DLPC) DNAs isolated from unaffected control, schizophrenic, and bipolar disorder brains for the presence of parvoviral sequences. This is the first investigator-blinded study to document the presence of parvoviral sequences in the DLPC by utilizing highly sensitive nested polymerase chain reaction (nPCR) and DNA sequencing. Of the overall sample, 6.7% to 12.5% were positive for AAV2, and 14.4% to 42.3% were positive for B19 sequences, with no statistical differences among subgroups. This is the first report to demonstrate the presence of human parvoviruses in a large cohort of adult DLPC, which underscores the need to gain a better insight into the basic biology of parvovirus-brain interactions, including mechanisms of infection and persistence.