Epidemiological and molecular characterization of a novel adenovirus of squirrel monkeys after fatal infection during immunosuppression.

Adenoviruses are a frequent cause of acute upper respiratory tract infections that can also cause disseminated disease in immunosuppressed patients. We identified a novel adenovirus, squirrel monkey adenovirus 1 (SqMAdV-1), as the cause of fatal infection in an immunocompromised squirrel monkey (Saimiri boliviensis) at the Keeling Center for Comparative Medicine and Research (KCCMR). Sequencing of SqMAdV-1 revealed that it is most closely related (80.4 % pairwise nucleotide identity) to the titi monkey (Plecturocebus cupreus) adenovirus (TMAdV). Although identified in the titi monkey, TMAdV is highly lethal in these monkeys, and they are not thought to be the natural host. While SqMAdV-1 is similar to other primate adenoviruses in size and genomic characteristics, a nucleotide polymorphism at the expected stop codon of the DNA polymerase gene results in a 126 amino acid extension at the carboxy terminus, a feature not previously observed among other primate adenoviruses. PCR testing and partial sequencing of 95 archived faecal samples from other squirrel monkeys (Saimiri boliviensis and Saimiri sciureus) housed at the KCCMR revealed the presence of three distinct, and apparently endemic species of adenoviruses. A grouping of ten squirrel monkey adenovirus variants has high similarity to SqMAdV-1. A single adenovirus variant (designated SqMAdV-3), detected in five monkeys, has similarity to tufted capuchin (Sapajus apella) adenoviruses. The largest group of adenovirus variants detected (designated SqMAdV-2.0-2.16) has very high similarity (93-99 %) to the TMAdV, suggesting that squirrel monkeys may be the natural host of the TMAdV.

Experimental Zika Virus Infection of Neotropical Primates.

The establishment of a sylvatic reservoir of Zika virus (ZIKV) in the Americas is dependent on the susceptibility of primates of sufficient population density, the duration and magnitude of viremia, and their exposure to the human mosquito-borne transmission cycle. To assess the susceptibility of squirrel (Saimiri sp.) and owl monkeys (Aotus sp.) to infection, we inoculated four animals of each species with ZIKV from the current epidemic. Viremia in the absence of detectible disease was observed in both species and seroconversion occurred by day 28. ZIKV was detected in the spleen of three owl monkeys: one at 7 days postinoculation (dpi) and two at 14 dpi. This study confirms the susceptibility to ZIKV infection of two Neotropical primate species that live in close proximity to humans in South America, suggesting that they could support a widespread sylvatic ZIKV cycle there. Collectively, establishment of a ZIKV sylvatic transmission cycle in South America would imperil eradication efforts and could provide a mechanism for continued exposure of humans to ZIKV infection and disease.

Endemic Viruses of Squirrel Monkeys (Saimiri spp.).

Nonhuman primates are the experimental animals of choice for the study of many human diseases. As such, it is important to understand that endemic viruses of primates can potentially affect the design, methods, and results of biomedical studies designed to model human disease. Here we review the viruses known to be endemic in squirrel monkeys (Saimiri spp.). The pathogenic potential of these viruses in squirrel monkeys that undergo experimental manipulation remains largely unexplored but may have implications regarding the use of squirrel monkeys in biomedical research.

Treatment of BK virus-associated nephropathy with CMX001 after kidney transplantation in a young child.

NC, with renal failure secondary to bilateral dysplastic kidneys, received an LRD renal transplant (tx) at 17 months of age. Her early post-tx course was complicated by persistently elevated blood polyoma BK virus DNA loads. A protocol biopsy at six months post-transplant revealed BKVAN. Blood viral loads did not respond to decreased immunosuppression or treatment with ciprofloxacin and leflunomide. Six months post-tx, her serum creatinine began to rise and we sought experimental therapy to prevent the loss of her graft. At seven months post-tx, with FDA approval under an eIND, the patient was started on a 36-wk course of treatment with the investigational drug. The patient is now more than 24 months after stopping treatment with CMX. BKV viral DNA loads remain at low, but still detectable levels. Urine viral loads have declined, but remain elevated. EBV DNA loads become undetectable. The patient's serum creatinine has declined back to a baseline of 0.5-0.7 mg/dL and has been stable for two yr. Renal function was preserved in association with the use of CMX001 to treat BKV nephropathy in a young pediatric kidney transplant recipient. There were no serious adverse events associated with the use of CMX001. This novel medication may be of value in the treatment of BKVAN in pediatric renal transplant recipients.

Serum biomarkers in head and neck squamous cell cancer.

IMPORTANCE: Serum biomarkers may be useful in the evaluation of suspected head and neck squamous cell cancer (HNSCC) and as indicators of treatment success or failure in adjuvant and chemopreventive clinical trials. OBJECTIVE: To determine serum cytokine and chemokine concentrations altered in patients with HNSCC compared with healthy volunteers to identify potential biomarkers. DESIGN, SETTING, AND PARTICIPANTS: A retrospective experimental laboratory study at Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport. Serum samples from 50 patients with stages II, III, and IV HNSCC and 20 healthy volunteers were available for study. Primary tumor sites represented in the patient group included the nasal cavity, oral cavity, oropharynx, hypopharynx, and larynx. INTERVENTIONS: Following institutional review approval and written informed consent, blood samples were drawn from patients. No intervention, to include any kind of diagnostic workup or treatment, was provided to patients during the course of this study. MAIN OUTCOMES AND MEASURES: The main outcome measures were the quantification of cytokine and chemokine concentrations in serum samples. Luminex multiplex panel technology was used for simultaneous measurement of 18 analytes, including fibroblast growth factor 2, granulocyte-macrophage colony-stimulating factor, growth-related oncogene, interferon (IFN)-γ, interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, inducible protein (IP)-10, soluble CD40 ligand, tumor necrosis factor, and vascular endothelial growth factor. RESULTS: The serum samples of patients with HNSCC contained lower levels of IFN-γ (mean patient serum level, 6.08 pg/mL, compared with the mean control level, 26.20 pg/mL; P = .004), IL-13 (mean patient serum level, 2.85 pg/mL, compared with the control mean level, 7.23 pg/mL; P = .02), and macrophage inflammatory protein-1ß (MIP-1ß) (mean patient serum level, 14.91 pg/mL, compared with the mean control level, 28.98 pg/mL; P = .004), and elevated levels of IP-10 (mean patient serum level, 359.24 pg/mL, compared with mean control level, 216.40 pg/mL; P = .04). All other markers tested were not significantly different between patients with cancer and controls. CONCLUSIONS AND RELEVANCE: This pilot study demonstrated a significant decrease in serum IFN-γ, IL-13, and MIP-1ß levels and a significant elevation of serum IP-10 concentration in patients with HNSCC, irrespective of primary tumor site. If validated in larger, independent studies, these serum biomarkers may be useful in the diagnosis and treatment of HNSCC. In the future, a defined, multianalyte screening panel could facilitate early diagnosis of HNSCC, allowing for earlier treatment and thereby reducing patient mortality.

Dynamics of urinary polyomavirus shedding in healthy adult women.

The hypothesis was examined that physiologic variation of estrogen concentrations during the menstrual cycle can provoke BK virus (BKV) excretion. BKV and JCV viral loads were determined in urine specimens obtained almost daily from 20 healthy, non-pregnant women over 2 months. Asymptomatic urinary shedding of BKV was observed in 123 (12.0%) of 1,021 specimens from 11 (55%) study subjects. Two subjects excreted JCV in their urine, with one subject excreting detectable JCV in all urine specimens. Analysis of 36 complete menstrual cycles revealed no difference in the prevalence of BKV excretion between pre-ovulatory and post-ovulatory phases of the menstrual cycle. The unexpected day-to-day variability in BKV excretion suggests that as yet unidentified factors may contribute to the periodic shedding of BKV by healthy women.

Dynamics of pregnancy-associated polyomavirus urinary excretion: a prospective longitudinal study.

Asymptomatic polyomaviruria of pregnancy has been documented in point prevalence studies, but little attention has been given to the dynamics of polyomavirus excretion during pregnancy because of its benign course. We tested the hypothesis that the frequency and/or magnitude of polyomavirus excretion would increase as pregnancy progresses. Urine specimens were obtained prospectively from 179 healthy women during uncomplicated pregnancies and 37 healthy non-pregnant women. Real-time polymerase chain reaction was used to determine BK virus (BKV) and JC virus (JCV) viral loads in urine, blood, and rectal and vaginal swabs collected during routine obstetric and gynecologic clinic visits. Asymptomatic urinary shedding of BKV and/or JCV was observed in 384 (48.0%) of 800 specimens from 100 (55.8%) pregnant women. BKV excretion was more common in pregnant than non-pregnant women (41.3% vs. 13.5%, P = 0.0026). The frequency of JCV excretion was no different in pregnant compared to non-pregnant women. The frequency and magnitude of polyomavirus shedding did not vary with gestational age. Post-partum shedding of BKV, but not JCV, rapidly decreased to undetectable levels. Pregnancy-associated BKV excretion begins early in pregnancy and terminates rapidly post-partum. Neither the frequency nor magnitude of BKV or JCV shedding increased with pregnancy progression. Further study into the host factors that regulate pregnancy-associated BKV excretion may allow identification of the host factors that predict susceptibility to BKV-associated diseases in immune compromised patients.