Viral infections after allogeneic hematopoietic stem cell transplant

Taneja, Alankrita; Chewning, Joseph H.; Saad, Ayman

doi:10.1002/acg2.43

Cited by 4 publications

(4 citation statements)

References 140 publications

(159 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatment of viral disease in transplant patients is a prime example. These immunosuppressed patients have heightened susceptibility to environmental pathogens as well as adventitious agents traveling with donor tissues or resident in the recipient, including herpesviruses, polyomaviruses, respiratory viruses, hepadnaviruses, and emerging viruses ( 8 , 9 , 89 , 90 ). We have already determined that several of these viral agents are inhibited by FLS-359, including HCMV ( Figure 4 ), which continues to threaten transplant recipients in spite of effective direct-acting therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, broad-spectrum HTAs have potential to provide a rapid therapeutic solution at the onset of a pandemic, reducing the time between novel virus identification and pharmacological intervention ( 6 , 7 ). Beyond this periodic need, HTAs can treat patients at risk for infection with viruses of different families, such as transplant patients who are at elevated risk for herpesvirus, paramyxovirus, polyomavirus, hepadnavirus, and coronavirus infections during immunosuppressive therapy ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An allosteric inhibitor of sirtuin 2 deacetylase activity exhibits broad-spectrum antiviral activity

Roche,

Remiszewski,

Todd

et al. 2023

Journal of Clinical Investigation

View full text Add to dashboard Cite

Most drugs used to treat viral disease target a virus-coded product. They inhibit a single virus or virus family, and the pathogen can readily evolve resistance. Host-targeted antivirals can overcome these limitations. The broad-spectrum activity achieved by host targeting can be especially useful in combating emerging viruses and for treatment of diseases caused by multiple viral pathogens, such as opportunistic agents in immunosuppressed patients. We have developed a family of compounds that modulate sirtuin 2, an NAD + -dependent deacylase, and now report the properties of a member of that family, FLS-359. Biochemical and x-ray structural studies show that the drug binds to sirtuin 2 and allosterically inhibits its deacetylase activity. FLS-359 inhibits the growth of RNA and DNA viruses, including members of the coronavirus, orthomyxovirus, flavivirus, hepadnavirus, and herpesvirus families. FLS-359 acts at multiple levels to antagonize cytomegalovirus replication in fibroblasts, causing modest reductions in viral RNAs and DNA, together with a much greater reduction in infectious progeny, and it exhibits antiviral activity in humanized mouse models of infection. Our results highlight the potential of sirtuin 2 inhibitors as broad-spectrum antivirals and set the stage for further understanding of how host epigenetic mechanisms impact the growth and spread of viral pathogens.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An allosteric inhibitor of sirtuin 2 deacetylase activity exhibits broad-spectrum antiviral activity

Roche,

Remiszewski,

Todd

et al. 2023

Journal of Clinical Investigation

View full text Add to dashboard Cite

show abstract

“…Viral infection or reactivation increases morbidity in hematopoietic stem cell transplant (HSCT) recipients, particularly after allogeneic transplantation including herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein Barr virus (EBV) and human herpes virus 6 (HHV-6) [ 1 , 2 ]. HHV-6 is part of to the β-herpesvirus subfamily.…”

Section: Introductionmentioning

confidence: 99%

Human herpesvirus-6 in hematopoietic stem cell transplant recipients: a prospective cohort study in Egypt

Raouf

Ouf

Elsorady

et al. 2023

Virol J

View full text Add to dashboard Cite

Background Immunocompromised patients face reactivation of latent viruses that increase the risk of morbidity. Aim The study aimed to detect human herpes virus 6 (HHV-6) reactivation among allogeneic (allo) and autologous (auto) hematopoietic stem cell transplant (HSCT) recipients and to correlate potentially attributed clinical manifestations to HHV-6 DNA plasma level. Methods A prospective study included all (forty) patients undergoing allo and auto-HSCT from Jan 2020 till June 2022. Plasma samples were collected for HHV-6 serology, and for HHV-6 quantitative PCR at post-transplantation weeks 2, 4, 6. Demographic and clinical data were recorded. Results Out of 40 peripheral blood stem cell transplant (PBSCT) recipients, 34 (85%) were HHV-6 IgG positive pre-HSCT. Of which, fourteen patients (14/34, 41.2%) showed positive HHV-6 DNaemia. HHV-6 DNAemia (15/40, 37.5%) was significantly higher among allo (8/12, 66.7%) versus auto (7/28, 25%) HSCT recipients (p = 0.030). Patients with HHV-6 DNAemia developed fever, delayed engraftment and bone marrow suppression in 6/15, 40%, thrombocytopenia (5/15, 33.3%), rash and pneumonitis (2/15, 13.3%), acute GVHD (aGVHD) (1/15, 6.7%). HHV-6 DNAemia ranged from 101 to 102,000 copies/mL. Univariate analysis identified conditioning with busulfan–cyclophosphamide as a significant risk (p = 0.043), while receiving BEAM protocol was a protective factor (p = 0.045). In multivariate analysis, receiving BEAM protocol retained significance (p = 0.040). Conclusion Frequent HHV-6 reactivation was detected after HSCT, especially in allo-HSCT recipients with clinical manifestations which could not be otherwise explained. To our best knowledge this is the first study of HHV6 reactivation in HSCT recipients from Egypt. Raising awareness for HHV-6 reactivation manifestations and screening in HSCT recipients could be lifesaving.

show abstract

“…In patients with immunodeficiencies, especially severe combined immunodeficiencies, fatality rates from severe and recurrent pulmonary ADV infections as well as disseminated disease have been reported to be up to 55% [ 1 , 21 ]. High-level HHV6 reactivation after allogeneic HSCT has been described in 30–50% of recipients [ 22 , 23 ]. BKV and JCV viremia occur in 54% and 25% of HSCT recipients, respectively, JCV viruria in 3.8–40% of kidney transplant patients, and BKV-induced nephropathy in 5.3% of the patients [ 17 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Antiviral T-Cell Frequencies in a Healthy Population: Reference Values for Evaluating Antiviral Immune Cell Profiles in Immunocompromised Patients

et al. 2022

View full text Add to dashboard Cite

Viral infections and reactivations are major causes of morbidity and mortality after hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) as well as in patients with immunodeficiencies. Latent herpesviruses (e.g., cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6), lytic viruses (e.g., adenovirus), and polyomaviruses (e.g., BK virus, JC virus) can cause severe complications. Antiviral drugs form the mainstay of treatment for viral infections and reactivations after transplantation, but they have side effects and cannot achieve complete viral clearance without prior reconstitution of functional antiviral T-cell immunity. The aim of this study was to establish normal ranges for virus-specific T-cell (VST) frequencies in healthy donors. Such data are needed for better interpretation of VST frequencies observed in immunocompromised patients. Therefore, we measured the frequencies of VSTs against 23 viral protein-derived peptide pools from 11 clinically relevant human viruses in blood from healthy donors (n = 151). Specifically, we determined the VST frequencies by interferon-gamma enzyme-linked immunospot assay and classified their distribution according to age and gender to allow for a more specific evaluation and prediction of antiviral immune responses. The reference values established here provide an invaluable tool for immune response evaluation, intensity of therapeutic drugs and treatment decision-making in immunosuppressed patients. This data should make an important contribution to improving the assessment of immune responses in immunocompromised patients.

show abstract

Viral infections after allogeneic hematopoietic stem cell transplant

Cited by 4 publications

References 140 publications

An allosteric inhibitor of sirtuin 2 deacetylase activity exhibits broad-spectrum antiviral activity

An allosteric inhibitor of sirtuin 2 deacetylase activity exhibits broad-spectrum antiviral activity

Human herpesvirus-6 in hematopoietic stem cell transplant recipients: a prospective cohort study in Egypt

Antiviral T-Cell Frequencies in a Healthy Population: Reference Values for Evaluating Antiviral Immune Cell Profiles in Immunocompromised Patients

Contact Info

Product

Resources

About