Biomedical subjects

Raphael P Viscidi

Publications and source records attributed to Raphael P Viscidi.

At least 19 recordsLinked to original sources

PubMed2007

Seroprevalence of human papillomavirus types 16 and 18 in the general population in Taiwan: implication for optimal age of human papillomavirus vaccination.

BACKGROUND: The optimal age for administration of recently approved prophylactic human papillomavirus (HPV) vaccines remains undetermined. OBJECTIVES: The aim of the study was to explore the age-specific seroprevalence of HPV 16 and 18 in the general population to design an HPV vaccination campaign for Taiwan. STUDY DESIGN: HPV seroprevalence was assessed by virus-like particle (VLP)-based ELISA in 1702 plasma samples collected in 1999. RESULTS: The sample population consisted of 1000 (58.8%) females and 702 (41.2%) males; age ranged from 17 days to 86 years. The age-specific distributions reveal a significant rise in HPV 16 seropositivity commencing at 19-25 years of age and peaking at >60 years. The trend of seropositivity increase with age was also highly significant for HPV 18 (P(Trend)<0.0001). Males had lower overall seroprevalence in gender comparison (7.6% versus 3.85% for HPV 16, 3.9% versus 2.71% for HPV 18), were older at seroconversion (19-25 years versus 26-30 years) with a more obvious seropositivity nadir in middle age. CONCLUSION: The age-specific seroprevalence of HPV 16 and 18 increases in young adults after the age of 18 years, with gender distribution varying. We conclude that the optimal age for universal HPV vaccination in Taiwan is 15 years or below.

Adolescent↗

PubMed2006

Temporal trends in gonococcal population genetics in a high prevalence urban community.

Molecular evolutionary studies can provide insights into the spread of infectious diseases and inform infection control measures. We performed a population genetic analysis of gonococcal isolates obtained over a 15-year interval in Baltimore, MD, where gonorrhea is highly prevalent. Categorical analysis of genetic differentiation revealed temporal structuring of the gonococcal population. The use of a new method to determine the historical demography of Neisseria gonorrhoeae from sequence data showed a strong correlation with trends in the number of reported cases of N. gonorrhoeae. The historical trends may also reflect the influence of social and demographic factors and the impact of antimicrobial resistance on the molecular epidemiology of gonorrhea in Baltimore over the past 2 decades. The strong correlation between the population genetic inferences over the last 20 years and the demographic data collected over the same time period demonstrates the utility of these approaches for the accurate inference of complex population dynamics using multilocus sequence data. The real time application of population genetic analysis can provide sentinel data on gonococcal prevalence, antibiotic resistance patterns and changing epidemiology of gonococcal infections.

Adult↗

PubMed2006

Vaccination of healthy volunteers with human papillomavirus type 16 L2E7E6 fusion protein induces serum antibody that neutralizes across papillomavirus species.

Oncogenic human papillomavirus (HPV) infection is a necessary cause of cervical cancer. Therefore, vaccination to prevent or eliminate HPV infection could reduce the incidence of cervical cancer. A fusion protein comprising HPV16 L2, E6, and E7 is a candidate combination preventive and therapeutic HPV vaccine. The L1- and L2-specific and neutralizing serum antibody titers and peripheral blood mononucleocyte antigen-specific proliferative responses generated by vaccination thrice at monthly intervals with HPV16 L2E7E6 were compared in two studies: a phase I randomized double-blind placebo controlled dose escalation trial in 40 healthy volunteers and a phase II trial of HPV16 L2E7E6 at the maximum dose in 29 women with high-grade anogenital intraepithelial neoplasia (AGIN). Vaccination of healthy volunteers induced L2-specific serum antibodies that were detected 1 month after the final vaccination (P(binomial) < 0.001). There was a significant trend to seroconversion for HPV16 and HPV18 neutralizing antibodies with increasing vaccine dose (P = 0.006 and P = 0.03, respectively). Seroconversion for HPV18 neutralizing antibodies showed a significant positive trend with increasing dose (P = 0.03) and was associated with seroconversion for HPV16 neutralizing antibodies (P(exact) = 0.04). The antigen-specific proliferative response of vaccinated healthy volunteers also showed a significant trend with increasing vaccine dose (P = 0.04). However, AGIN patients responded less effectively to vaccination than healthy patients for induction of HPV16 L2-specific antibody (P < 0.001) and proliferative responses (P < 0.001). Vaccination of healthy volunteers thrice with 533-mug HPV16 L2E7E6 at monthly intervals induced L2-specific serum antibodies that neutralized across papillomavirus species. Responses in AGIN patients were infrequent.

Adult↗

PubMed2006

Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1.

BACKGROUND: Genetic diversity of the human immunodeficiency virus type 1 (HIV-1) population within an individual is lost during transmission to a new host. The demography of transmission is an important determinant of evolutionary dynamics, particularly the relative impact of natural selection and genetic drift immediately following HIV-1 infection. Despite this, the magnitude of this population bottleneck is unclear. RESULTS: We use coalescent methods to quantify the bottleneck in a single case of homosexual transmission and find that over 99% of the env and gag diversity present in the donor is lost. This was consistent with the diversity present at seroconversion in nine other horizontally infected individuals. Furthermore, we estimated viral diversity at birth in 27 infants infected through vertical transmission and found there to be no difference between the two modes of transmission. CONCLUSION: Assuming the bottleneck at transmission is selectively neutral, such a severe reduction in genetic diversity has important implications for adaptation in HIV-1, since beneficial mutations have a reduced chance of transmission.

Bayes Theorem↗

PubMed2006

Phylogenomics and molecular evolution of polyomaviruses.

We provide in this chapter an overview of the basic steps to reconstruct evolutionary relationships through standard phylogeny estimation approaches as well as network approaches for sequences more closely related. We discuss the importance of sequence alignment, selecting models of evolution, and confidence assessment in phylogenetic inference. We also introduce the reader to a variety of software packages used for such studies. Finally, we demonstrate these approaches throughout using a data set of 33 whole genomes of polyomaviruses. A robust phylogeny of these genomes is estimated and phylogenetic relationships among the polyomaviruses determined using Bayesian and maximum likelihood approaches. Furthermore, population samples of SV40 are used to demonstrate the utility of network approaches for closely related sequences. The phylogenetic analysis suggested a close relationship among the BK viruses, JC viruses, and SV40 with a more distant association with mouse polyomavirus, monkey polymavirus (LPV) and then avian polyomavirus (BFDV).

Computational Biology↗

PubMed2006

Serological cross reactivity between polyomavirus capsids.

Multiple methods have been used to measure antibodies to polyomavirus virions. In order to have a common method for all polyomaviruses, we developed enzyme immunoassays (EIAs) using virus-like-particles (VLPs) produced in the baculovirus expression system. We tested serum samples from humans and rhesus macaques in VLP-based EIAs for the two human polyomaviruses, BK and JC virus, and two nonhuman primate polyomaviruses, simian virus 40 (SV40) and lymphotropic polyomavirus (LPV). Rhesus sera exhibited low level reactivity to BK and JC, and approximately 10 and 15% of human sera showed low level reactivity to SV40 and LPV, respectively. Competitive inhibition assays with VLP protein demonstrated that the reactivity of rhesus sera against BK and JC VLPs was blocked by both SV40 and the respective human polyomavirus, indicating that the BK and JC assays were detected cross-reacting antibodies. Similarly, the reactivity of the majority of human sera to SV40 was blocked by both SV40 and BK or JC, demonstrating that the SV40 reactivity of human sera is largely due to cross reacting BK and JC antibodies. In contrast, the reactivity of human sera to LPV VLPs was blocked by LPV but not by BK or JC, providing serological evidence for an unknown human polyomavirus related to LPV. SV40 and LPV VLP-based EIAs and competitive inhibition assays with heterologous VLPs provide tools for seroepidemiological studies of possible SV40 and LPV-like infections of humans.

Antibodies, Viral↗

PubMed2006

Immunoglobulin G, A, and M responses to BK virus in renal transplantation.

Immunoglobulin G (IgG), IgA, and IgM antibodies were measured in serum samples from 71 organ donors, 81 kidney transplant recipients at transplantation, and 67 patients during the posttransplant period by using a virus-like particle-based enzyme-linked immunosorbent assay (ELISA). BK virus (BKV) and JC virus DNA were detected in urine and plasma by real-time PCR. IgG antibodies to BKV were demonstrated in the majority (80.3 to 100%) of patients irrespective of clinical category, but titers were highest in patients with active viral replication. IgA antibodies were present with greater frequency (72.7 to 81.3% versus 0 to 23.6%; P < 0.001) and higher titer (mean optical density, 0.11 to 0.15 versus 0.05 to 0.08; P < 0.001) in patients who were BKV DNA positive than those who were BKV DNA negative. IgM antibodies showed a similar pattern of reactivity but lower frequency in the setting of active viral replication (9.1 to 43.7% versus 0 to 1.4%; P < 0.001). A rise in IgG level of >0.577 optical density (OD) units or a rise in IgA or IgM level of >0.041 OD units was strongly associated with active viral replication. Urine viral load showed a positive correlation with IgM titer (r = 0.22) but a negative correlation with IgG titer (r = -0.28) and IgA titer (r = -0.1). Chronic dialysis patients typically did not have serologic or virologic evidence of active BKV infection. Anti-BKV titers did not rise in patients with JC viruria. In conclusion, measurement of anti-BKV antibody titer and class response can be used to detect the onset of viral replication. ELISAs can be quite specific despite considerable sequence homology between BK virus and JC virus.

Adolescent↗

PubMed2006

Serological detection of human papillomavirus type 16 infection in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women.

Serial measurement of antibodies has not been used to provide evidence of active viral replication of human papillomavirus (HPV). Serum specimens from sequential study visits contributed by 642 human immunodeficiency virus (HIV)-positive and 116 HIV-negative participants enrolled in the Women's Interagency HIV Study were used to detect significant rises in HPV type 16 (HPV-16) antibody levels. Factors associated with a significant rise were identified using multivariable logistic regression models with generalized estimating equations. Among HIV-positive women, 8.3% of 1,997 pairs showed antibody rises, compared to 6.1% of 361 pairs among HIV-negative women (P = 0.191). For HIV-positive women, rises were associated with current (odds ratio [OR], 23.4; P < 0.001) or past (OR, 8.9; P < 0.001) HPV-16 infection relative to never being HPV-16 infected and with CD4+ cell counts (OR per 100-cell increase, 0.8; P < 0.001) but not with sexual behavior. For HIV-negative women, rises were associated with past (OR, 10.9; P = 0.033) HPV-16 infection relative to no HPV-16, current cigarette smoking (OR, 5.0; P = 0.029) relative to no smoking history, and having 6 to 10 lifetime sexual partners compared to 0 to 5 partners (OR, 9.9; P = 0.036). Serial measurement of HPV-16 serum antibodies is a useful tool for identifying active HPV-16 viral replication. Rises among HIV-positive women may more often result from reactivation of a latent HPV infection in the context of HIV-induced immunosuppression, while rises among HIV-negative women may more often result from reinfection with HPV.

Antibodies, Viral↗

PubMed2006

Comparing phylogenetic codivergence between polyomaviruses and their hosts.

Seventy-two full genomes corresponding to nine mammalian (67 strains) and two avian (5 strains) polyomavirus species were analyzed using maximum likelihood and Bayesian methods of phylogenetic inference. Our fully resolved and well-supported (bootstrap proportions > 90%; posterior probabilities = 1.0) trees separate the bird polyomaviruses (avian polyomavirus and goose hemorrhagic polyomavirus) from the mammalian polyomaviruses, which supports the idea of spitting the genus into two subgenera. Such a split is also consistent with the different viral life strategies of each group. Simian (simian virus 40, simian agent 12 [Sa12], and lymphotropic polyomavirus) and rodent (hamster polyomavirus, mouse polyomavirus, and murine pneumotropic polyomavirus [MPtV]) polyomaviruses did not form monophyletic groups. Using our best hypothesis of polyomavirus evolutionary relationships and established host phylogenies, we performed a cophylogenetic reconciliation analysis of codivergence. Our analyses generated six optimal cophylogenetic scenarios of coevolution, including 12 codivergence events (P < 0.01), suggesting that Polyomaviridae coevolved with their avian and mammal hosts. As individual lineages, our analyses showed evidence of host switching in four terminal branches leading to MPtV, bovine polyomavirus, Sa12, and BK virus, suggesting a combination of vertical and horizontal transfer in the evolutionary history of the polyomaviruses.

Animals↗

PubMed2006

Prediagnostic circulating antibodies to JC and BK human polyomaviruses and risk of non-Hodgkin lymphoma.

Viral infections have been associated with increased risk of non-Hodgkin's lymphoma (NHL). We conducted a nested case-control study to investigate the association between prediagnostic serum antibodies to the human polyomaviruses, JC (JCV) and BK (BKV), and subsequent risk of NHL. Two research serum banks were established in Washington County, Maryland, in 1974 and 1989, with the collection of blood samples from >45,000 volunteers. Incident NHL cases diagnosed through 2002 (n = 170) were identified among participants by linkage to population-based cancer registries. Two controls were matched to each case (n = 340) on age, sex, and blood draw date. Prediagnostic IgG antibodies to JCV and BKV were measured using virus-like particle ELISA. Associations between JCV and BKV antibody seropositivity and NHL were estimated using conditional logistic regression. Overall, neither antibodies to JCV [odds ratio (OR), 0.83; 95% confidence interval (95% CI), 0.56-1.23] nor BKV (OR, 0.98; 95% CI, 0.64-1.48) were associated with an increased risk of NHL. Results were similar after stratification by NHL subtype or induction period and adjustment for EBV seropositivity. Among those who donated blood in both 1974 and 1989, an increase in JCV antibody levels over time was associated with a 4-fold increased risk of NHL compared with a steep decline in antibody levels (OR, 4.59; 95% CI, 1.30-16.25; P(trend) = 0.02). Whereas JCV seropositivity was not associated with NHL overall, the finding of an increased risk of NHL associated with increasing antibody levels among those who were seropositive at baseline warrants further research into factors influencing reactivation of JCV infection.

Adult↗

PubMed2005

Antibodies to JC and BK viruses among persons with non-Hodgkin lymphoma.

Two related polyomaviruses, JC virus (JCV) and BK virus (BKV), commonly cause lifelong infections in humans, with periodic reactivation manifesting as viral shedding in urine. Because JCV can infect lymphocytes and cause chromosomal damage, it is a plausible candidate to cause non-Hodgkin lymphoma (NHL). To test this hypothesis, we measured IgG antibodies to JCV and BKV capsids using a virus-like particle enzyme immunoassay in 3 separate groups of subjects. First, in a U.S. population-based case-control study of NHL (724 cases, 622 controls), we found lower JCV antibody levels in cases than controls (median optical density = 0.12 vs. 0.21, p < 0.0001); likewise, JCV seroprevalence was lower in cases (49% vs. 59%, adjusted odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.56-0.87). In contrast, BKV antibody levels did not differ between groups. Second, we found that JCV and BKV antibody levels changed little over time among 24 NHL patients receiving chemotherapy. Third, we evaluated 126 homosexual men, of whom 46 were shedding JCV and 14 were shedding BKV in urine. Antibody levels were much higher in shedders than non-shedders (JCV: median optical density = 0.67 vs. 0.07, p < 0.0001; BKV: 0.87 vs. 0.40, p = 0.003), indicating that these antibodies are a marker for viral replication. Because no deficit of BKV antibody was seen in NHL cases, and because antibody levels did not change materially with chemotherapy, we suggest that the lower levels of JCV antibody observed in NHL patients may not be due entirely to a disease or treatment effect. Additional research is needed to determine whether JCV replication is decreased in individuals with NHL and whether these findings are consistent with an etiologic role for JCV in NHL.

Adult↗

PubMed2005

B lymphocyte activation by human papillomavirus-like particles directly induces Ig class switch recombination via TLR4-MyD88.

Vaccination with human papillomavirus type 16 (HPV16) L1 virus-like particles (VLP) induces both high titer neutralizing IgG and protective immunity. Because protection from experimental infection by papillomavirus is mediated by neutralizing IgG, we sought the mechanisms that trigger humoral immunity to HPV16 L1 VLP. We find that HPV16 L1 VLP bind to murine B lymphocytes thereby inducing activation-induced cytidine deaminase expression and Ig class switch recombination to cause the generation of IgG. HPV16 L1 VLP also activate production of proinflammatory factors IFN-alpha, IL-6, MIP-1alpha, RANTES, and KC, up-regulate the expression of costimulatory molecules by naive B cells, and increase the B1 B cell subpopulation. These B cell responses to HPV16 L1 VLP are dependent upon MyD88. Although MyD88(-/-) B cells produce only mu transcript after exposure to HPV16 L1 VLP, MyD88(+/+) B cells express alpha, gamma, and mu Ig H chain and activation-induced cytidine deaminase transcripts. Notably, TLR4 mutant C3H/HeJ mice exhibited significantly reduced HPV16 VLP-specific IgG1, IgG2a, IgG2b, and IgG3 titers after vaccination as compared with the control C3H/HeOuJ mice. HPV16 L1 VLP directly activated class switch recombination and costimulatory molecule expression by B cells of C3H/HeOuJ mice but not C3H/HeJ mice. Thus HPV16 L1 VLP directly activate B cells to induce CD4(+) T cell independent humoral immune responses via TLR4- and MyD88-dependent signaling.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Population genetics of Neisseria gonorrhoeae in a high-prevalence community using a hypervariable outer membrane porB and 13 slowly evolving housekeeping genes.

Baltimore, Md., is an urban community with a high prevalence of Neisseria gonorrhoeae. Due to partially protective immune responses, introduction of new strains from other host populations, and exposure of N. gonorrhoeae to antibiotics, the phenotypic and genotypic characteristics of the circulating strains can fluctuate over time. Understanding the overall genetic diversity and population structure of N. gonorrhoeae is essential for informing public health interventions to eliminate this pathogen. We studied gonococci population genetics in Baltimore by analyzing a hypervariable and strongly selected outer membrane porB gene and 13 slowly evolving and presumably neutral housekeeping genes (abcZ, adk, aroE, fumC, gdh, glnA, gnd, pdhC, pgm, pilA, ppk, pyrD, and serC) in 204 isolates collected in 1991, 1996, and 2001 from male and female patients of two public sexually transmitted diseases clinics. Genetic diversity (), recombination (C), growth (g), population structure, and adaptive selection under codon-substitution and amino acid property models were estimated and compared between these two gene classes. Estimates of the F(ST) fixation index and the chi(2) test of sequence absolute frequencies revealed significant temporal substructuring for both gene types. Baltimore's N. gonorrhoeae populations have increased since 1991 as indicated by consistent positive values of g. Female patients showed similar or lower levels of and C than male patients. Within the MLST housekeeping genes, levels of and C ranged from 0.001-0.013 and 0.000-0.018, respectively. Overall recombination seems to be the dominant force driving evolution in these populations. All loci showed amino acid sites and physicochemical properties under adaptive (or positive-destabilizing) selection, rejecting the generally assumed hypothesis of stabilizing selection for these MLST genes. Within the porB gene, protein I B showed higher and C values than protein I A. Directional positive selection possibly mediated by the immune system operates to a significant extent in the protein I sequences, as indicated by the distribution of the positively selected sites in the surface-exposed loops. Thirteen amino acid physicochemical properties seem to drive protein evolution of the PI porins in N. gonorrhoeae.

Amino Acid Sequence↗

PubMed2005

Population genetics of microbial pathogens estimated from multilocus sequence typing (MLST) data.

The inference of population recombination (rho), population mutation (Theta), and adaptive selection is of great interest in microbial population genetics. These parameters can be efficiently estimated using explicit statistical frameworks (evolutionary models) that describe their effect on gene sequences. Within this framework, we estimated rho and Theta using a coalescent approach, and adaptive (or destabilizing) selection under heterogeneous codon-based and amino acid property models in microbial sequences from MLST databases. We analyzed a total of 91 different housekeeping gene regions (loci) corresponding to one fungal and sixteen bacterial pathogens. Our results show that these three population parameters vary extensively across species and loci, but they do not seem to be correlated. For the most part, estimated recombination rates among species agree well with previous studies. Over all taxa, the rho/Theta ratio suggests that each factor contributes similarly to the emergence of variant alleles. Comparisons of Theta estimated under finite- and infinite-site models indicate that recurrent mutation (i.e., multiple mutations at some sites) can increase Theta by up to 39%. Significant evidence of molecular adaptation was detected in 28 loci from 13 pathogens. Three of these loci showed concordant patterns of adaptive selection in two to four different species.

Alleles↗

PubMed2005

BK virus-specific antibodies and BKV DNA in renal transplant recipients with BKV nephritis.

We evaluated twenty renal transplant subjects at various stages of BKV nephritis (BKVN) for BKV-specific IgG and IgM antibodies using ELISA technique and BKV-DNA using PCR. They were divided as early onset (n = 7), stabilizing (n = 3), resolved (n = 8) and late onset (n = 2) BKVN. BKV-specific antibodies and BKV-DNA were simultaneously determined. The mean BKV-specific IgG level in early onset and stabilizing BKVN were 64 and 39 EIA units, and were significantly lower than 138 EIA units seen in resolved BKVN, P = 0.007, P = 0.008. The mean BKV-specific IgM levels in stabilizing BKVN was higher than resolved BKVN (130 vs 51 EIA units), P = 0.006. Mean plasma BKV loads for each group were 955,925, 5642 and 42 copies/mL of plasma, respectively. Prospective study in six BKVN cases revealed mean IgG, IgM levels and BKV-DNA at the time of diagnosis of BKVN as 39, 110 EIA units and 586,758 copies/mL of plasma, respectively. After a mean period of 5.2 months, IgG level increased to 120 EIA units (p = 0.0058) and had no detectable viral copies in circulation. Recovery from BKVN and elimination of BKV is associated with the development of BKV-specific IgG antibodies and this provides insight into the role of humoral immunity to BKV in the pathogenesis of BKVN.

Adult↗

PubMed2005

Papillomavirus capsid mutation to escape dendritic cell-dependent innate immunity in cervical cancer.

Infection with oncogenic human papillomaviruses (HPVs), typified by HPV type 16 (HPV16), is a necessary cause of cervical cancer. Prophylactic vaccination with HPV16 L1 virus-like particles (VLPs) provides immunity. HPV16 VLPs activate dendritic cells and a potent neutralizing immunoglobulin G (IgG) response, yet many cervical cancer patients fail to generate detectable VLP-specific IgG. Therefore, we examined the role of the innate recognition of HPV16 L1 in VLP-induced immune responses and its evasion during carcinogenesis. Nonconservative mutations within HPV16 L1 have been described in isolates from cervical cancer and its precursor, high-grade cervical intraepithelial neoplasia (CIN). We determined the effect of mutations in L1 upon in vitro self-assembly into VLPs and their influence upon the induction of innate and adaptive immune responses in mice. Several nonconservative mutations in HPV16 L1 isolated from high-grade CIN or cervical carcinoma prevent self-assembly of L1 VLPs. Intact VLPs, but not assembly-defective L1, activate dendritic cells to produce proinflammatory factors, such as alpha interferon, that play a critical role in inducing adaptive immunity. Indeed, effective induction of L1-specific IgG1 and IgG2a was dependent upon intact VLP structure. Dendritic cell activation and production of virus-specific neutralizing IgG by VLPs requires MyD88-dependent signaling, although the L1 structure that initiates MyD88-mediated signaling is distinct from the neutralizing epitopes. We conclude that innate recognition of the intact L1 VLP structure via MyD88 is critical in the induction of high-titer neutralizing IgG. Tumor progression is associated with genetic instability and L1 mutants. Selection for assembly-deficient L1 mutations suggests the evasion of MyD88-dependent immune control during cervical carcinogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Antibody responses to simian virus 40 T antigen: a case-control study of non-Hodgkin lymphoma.

A possible role for SV40, a macaque polyomavirus, in non-Hodgkin lymphoma (NHL) in humans was raised recently by the reported detection of SV40 DNA in tumor tissue. Animals with SV40-induced tumors frequently produce high-level antibodies against T antigen, the SV40 oncoprotein. In this study, we assessed whether SV40 T antibody measured in humans supported a relationship between SV40 and NHL. Subjects were sampled from a U.S. population-based case-control study of NHL, according to presence of antibodies against capsids of SV40 and BK, a related human polyomavirus (n = 85 cases, n = 95 controls). T antibody was measured by enzyme immunoassay. We also evaluated serum specimens from SV40-infected and SV40-uninfected macaques (n = 19 and n = 8, respectively), SV40-uninfected hamsters (n = 5), and hamsters with SV40-induced tumors (n = 10). Hamsters with SV40-induced tumors all produced robust SV40 T antibody [median absorbance, 0.99), whereas SV40-uninfected hamsters and macaques had much lower levels (median absorbance, 0.05 and 0.04, respectively). NHL cases, controls, and SV40-infected macaques resembled these latter two groups, generally showing only low-level T antibody (median absorbance, 0.03, 0.04, and 0.04, respectively). Overall, only five cases (6%) and five controls (5%) had T antibody responses classified as seropositive (odds ratio, 1.2; 95% confidence interval, 0.3-4.6). Interestingly, all 10 humans with T antibody responses also showed antibody responses to BK capsid. We found no association between the presence of T antibody and NHL, arguing against SV40 as a cause of NHL. Infrequent and low-level T antibody responses among humans could represent cross-reactivity to BK virus T antigen.

Adult↗

PubMed2005

Markers of past infection with simian virus 40 (SV40) and risk of incident non-Hodgkin lymphoma in a Maryland cohort.

Simian virus 40 (SV40) genome sequences have been detected in human non-Hodgkin lymphoma (NHL) tissues, and past infection with SV40 may be a risk factor for NHL. We conducted a population-based nested case-control study to investigate the association between serum antibodies to SV40 and incident NHL. Two research serum banks were established in Washington County, MD, with >45,000 volunteers contributing blood samples collected in 1974 and 1989. Incident cases of NHL diagnosed through 2002 (n = 170) were identified among participants by linkage to population-based cancer registries. Two controls were matched to each case (n = 340) on age, sex, and date of blood draw. Circulating immunoglobulin G antibodies to SV40 were measured using virus-like particle (VLP) ELISA. Positive samples were tested for cross-reactivity with JC virus (JCV) and BK virus (BKV) through competitive inhibition assays. Associations between SV40 antibody seropositivity and NHL were estimated using conditional logistic regression. Whereas SV40 antibodies were detected by VLP ELISA in 15% of cases and 10% of controls [matched odds ratio (OR), 1.97; 95% confidence interval (95% CI), 1.03-3.76], the SV40 reactivity of 85% of the SV40 antibody-positive sera was decreased by adsorption with BKV and/or JCV VLPs. Antibodies specific for SV40 (not cross-reactive) were identified in only 1.8% of cases and 1.6% of controls (OR, 1.51; 95% CI, 0.41-5.52). Our findings suggest that past infection with SV40 is not associated with an increased risk of developing NHL.

Antibodies, Viral↗