Human adenovirus species in children with acute respiratory illnesses

Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound 16 (JMX0493) as a potent inhibitor of HAdV infection. Compound 16 displays submicromolar IC50 values, a higher selectivity index (SI > 100) and 2.5-fold virus yield reduction compared to our hit compound niclosamide. Moreover, unlike niclosamide, our mechanistic studies suggest that the antiviral activity of compound 16 against HAdV is achieved through the inhibition of viral particle escape from the endosome, which bars subsequent uncoating and the presentation of lytic protein VI.

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729. Improved Detection of Adenovirus with the FilmArray Respiratory Panel 2 Panel in a Pediatric Population

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.736 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S262-S262

Author(s):

Kathy Everhart ◽

Huanyu Wang ◽

Li Xu ◽

Amy Leber

Keyword(s):

Respiratory Infections ◽

Pediatric Population ◽

Human Adenovirus ◽

Fold Increase ◽

Clinical Samples ◽

Research Support ◽

Respiratory Illnesses ◽

Two Samples ◽

Type C ◽

Hospital Research

Abstract Background Human adenovirus (ADV) respiratory infections are associated with up to 8% of all identified viral causes of acute respiratory illnesses, especially among young children. They are therefore included as part of multiplex syndromic respiratory testing. Earlier versions of the FilmArray Respiratory Panel were targeted to genogroups B, C, and E. However, all adenovirus genogroups are associated with disease particularly in immunocompromised patients. Recently, a new version of the FilmArray Respiratory Panel 2 (RP2) has been FDA cleared with significant modifications to the adenovirus assay. The goal of this study was to compare the RP2 adenovirus assay to that of the previous version (RP1.7) and our laboratory-developed (LD) adenovirus PCR. Methods Analytical comparison: Ten stocks of know adenovirus serotypes representing genogroups A-F were diluted in M4 media and tested on RP2, RP1.7 and LD PCR to determine the relative limits of detection (LOD). Clinical comparison: A total of 423 pediatric nasopharyngeal samples were tested using RP2, RP1.7, adenovirus LD PCR. In addition we performed genotyping PCRs on most adenovirus positive samples based on the availability. Results Analytical evaluation revealed that for the 10 serotypes (18, 32, 7, 14, 5, 6, 20, 29, 4 and 40), RP2 showed at least 100-fold increase in sensitivity for six serotypes representing genogroups A, D and F. For B, C and E, the relative LODs were comparable. In the 423 clinical samples, there was an overall agreement of 94% between RP2 and RP1.7. Among those RP2+/RP1.7− samples (n = 20), 17 samples were confirmed ADV positive by LD PCR. They all had low viral burden (Ct values >30), among them nine samples had sole detections of adenovirus types A, D and F. Five samples were RP2-/RP1.7+, two samples were confirmed by LD PCR and both were type C. Overall, there was a 22% increase in Adenovirus with RP2 compared with RP1.7. Conclusion The RP2 adenovirus assay has enhanced inclusivity and lower LOD for all adenovirus genogroups in comparison to RP1.7. Coupled with its faster run time and additional targets, RP2 represents a significant improvement for the syndromic detection of respiratory infections. Disclosures A. Leber, Nationwide Children’s Hospital: Research Contractor, Research support.

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741. Impact of Adenovirus Co-detections on Illness Severity

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.748 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S266-S266

Author(s):

Varvara Probst ◽

Bhinnata Piya ◽

Laura Stewart ◽

Susan Gerber ◽

Brian Rha ◽

...

Keyword(s):

Medical Condition ◽

Human Adenovirus ◽

Illness Severity ◽

Inpatient Setting ◽

Hospital Inpatient ◽

Respiratory Pathogens ◽

Viral Pathogens ◽

Respiratory Illnesses ◽

Co Detection

Abstract Background Human adenovirus (AdV) is a common pathogen among children with acute respiratory illnesses (ARI) and is often associated with co-detection with other respiratory viral pathogens. We sought to compare demographic and clinical characteristics in children with ARI who had single-AdV vs. AdV-co-detection with other viruses. Methods Children <18 years with fever and/or ARI were enrolled in Vanderbilt Children’s Hospital inpatient setting from 2015 to 2018 and emergency department from 2016 to 2018. Interviews were conducted using standardized case report forms. Nose and throat swab specimens were collected and tested by RT-qPCR for common respiratory pathogens (AdV, RSV, HRV, hMPV, PIV1–4 and Influenza). Results Of 2,740 ARI cases, 174 were positive for AdV [88 (51%) single detection], with 53% male, 47% White, 36% Black, 30% Hispanic and median age of 17.2 months. Co-detected pathogens in AdV-positive specimens were RSV(15%), HRV(14%), influenza(5%), PIV1(1%), PIV2(0.6%), PIV3(1.7%), and PIV4(0.6%), hMPV(3%), >1 co-pathogens(9%). Subjects with single-AdV detection were more likely to have an underlying medical condition (42% vs. 24%, P < 0.05). Table 1 compares clinical presentation and severity of single-AdV and AdV-co-detection cases. Conclusion Patients with single-AdV detection were less likely to present with ARI symptoms and require oxygen, but were more likely to have underlying medical conditions compared with AdV-co-detection. Further studies to type AdV isolates will help elucidate the role of specific adenovirus types associated with co-detections and illness severity and inform epidemiological information for future vaccine initiatives. Disclosures J. V. Williams, Quidel: Board Member, Consulting fee. GlaxoSmithKline: Consultant, Consulting fee. N. B. Halasa, sanofi pasteur: Investigator, Research support. GSK: Consultant, Consulting fee. Moderna: Consultant, Consulting fee.

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237. Adenovirus Types in Children with Acute Respiratory Illnesses in Nashville Over Two Respiratory Seasons

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.312 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S135-S136

Author(s):

Varvara Probst ◽

Andrew Speaker ◽

Laura S Stewart ◽

Claudia Guevara ◽

Susan I Gerber ◽

...

Keyword(s):

Real Time ◽

Pediatric Population ◽

Human Adenovirus ◽

Respiratory Viruses ◽

Early Spring ◽

Hospital Inpatient ◽

Respiratory Illnesses ◽

Chart Abstraction ◽

Co Detection ◽

Nose And Throat

Abstract Background Human adenovirus (HAdV) types 1–7, 11, 14, 16, and 21 within species B, C, and E are commonly associated with acute respiratory illnesses (ARI) in children. We sought to compare demographics, clinical characteristics, and outcomes of HAdV types with children who presented with fever and/or respiratory symptoms. Methods Children < 18 years with fever and/or ARI seen at Vanderbilt Children’s Hospital inpatient and emergency department settings from December of 2016 to October of 2018 were enrolled. Interviews and chart abstraction were conducted. Mid-turbinate nose and throat swab specimens were collected and tested by real-time RT-PCR for common respiratory viruses including HAdV. HAdV molecular typing was performed by type-specific real-time PCR assays for types 1–7, 11, 14, 16, and 21 targeting the hexon gene using published methods. Results Of 5111 ARI cases, 206 (4%) were HAdV-positive with a median age of 16 months (IQR 9–30); 57% male, 47% White, 40% Black, 33% Hispanic, 20% admitted, and 24% of hospitalized required oxygen support. Of the 206, 186 (90%) were able to be typed with more than one types detected in 13 (7%) cases. Distribution of HAdV types among single detections (n = 173) is shown in Figure 1; HAdV-1 and HAdV-2 were most common. Children with HAdV-2 were younger (median age 12 months vs. 15 months (HAdV-1) and 59 months (all other types), P < 0.001), and those with HAdV-1 were less likely to be male (44% vs. 65% for both HAdV-2 and other types, P = 0.029). Figure 2 displays HAdV detections over time, with winter and early spring peaks. Co-detection with other respiratory viruses occurred in 47% of cases; the most common among typable HAdV were rhinovirus/enterovirus in 30/186 (16%) and RSV in 19/186 (10%). Distribution among HAdV types is shown in Figure 3. Conclusion HAdV-1 and HAdV-2 were more prevalent than other HAdV types over two respiratory seasons in the Nashville area with peak cases in December-March. Children with HAdV-1 and HAdV-2 had some demographic differences. Further studies with a larger sample size for HAdV typing are needed in the pediatric population to determine whether additional clinically-relevant differences between HAdV types exist. Disclosures All authors: No reported disclosures.

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Human Adenovirus Uptake by Preirnplantation Mouse Embryos

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100094607 ◽

1972 ◽

Vol 30 ◽

pp. 268-269

Author(s):

D. G. Chase ◽

W. Winters ◽

L. Piko

Keyword(s):

Hela Cells ◽

Human Adenovirus ◽

Mouse Embryos ◽

Equilibrium Density ◽

Cell Stage ◽

Virus Attachment ◽

Preimplantation Mouse Embryos ◽

Embryo Culture Medium ◽

Preimplantation Mouse ◽

Mouse Cells

Although the outlines of human adenovirus entry and uncoating in HeLa cells has been clarified in recent electron microscope studies, several details remain unclear or controversial. Furthermore, morphological features of early interactions of human adenovirus with non-permissive mouse cells have not been extensively documented. In the course of studies on the effects of human adenoviruses type 5 (AD-5) and type 12 on cultured preimplantation mouse embryos we have examined virus attachment, entry and uncoating. Here we present the ultrastructural findings for AD-5.AD-5 was grown in HeLa cells and purified by successive velocity gradient and equilibrium density gradient centrifugations in CsCl. After dialysis against PBS, virus was sedimented and resuspended in embryo culture medium. Embryos were placed in culture at the 2-cell stage in Brinster's medium.

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