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Puumala Hantavirus Infections Show Extensive Variation in Clinical Outcome

Antti Vaheri1, Teemu Smura1, Hanna Vauhkonen1

  • 1Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, Finland.

Viruses
|March 30, 2023
PubMed

Insights

Puumala hantavirus (PUUV) infection severity varies widely. Genetic factors like HLA alleles and tumor necrosis factor (TNF) influence outcomes, but the exact reasons for this variation remain unclear.

Area of Science:

  • Virology
  • Immunogenetics
  • Infectious Diseases

Background:

  • Puumala hantavirus (PUUV) causes a spectrum of disease, from asymptomatic infections to severe hemorrhagic fever with renal syndrome (HFRS).
  • Acute kidney injury (AKI), termed acute hemorrhagic tubulointerstitial nephritis, is common in hospitalized PUUV patients.
  • The significant variation in clinical outcomes for PUUV infection is not fully understood.

Purpose of the Study:

  • To explore the factors contributing to the wide variation in clinical outcomes of Puumala hantavirus (PUUV) infection.
  • To investigate the role of host genetic factors, such as human leukocyte antigen (HLA) alleles and tumor necrosis factor (TNF) gene variants, in PUUV disease severity.
  • To identify potential biomarkers, including plasma glucose concentration, associated with PUUV infection severity.

Main Methods:

  • Review of existing literature on clinical outcomes, genetic associations, and biomarkers in PUUV infection.
  • Analysis of associations between specific human leukocyte antigen (HLA) alleles (B*08, DRB1*0301, B*27) and disease severity.
  • Examination of the role of tumor necrosis factor (TNF) gene and complement system (C4A) in PUUV pathogenesis.
  • Assessment of the correlation between plasma glucose levels and clinical manifestations like capillary leakage, thrombocytopenia, inflammation, and AKI.

Main Results:

  • Specific HLA alleles (B*08, DRB1*0301) are linked to severe PUUV infection, while B*27 is associated with a benign course.
  • Genetic factors related to TNF and C4A may play a role in disease variation.
  • Plasma glucose concentration is a newly identified factor associated with the severity of capillary leakage, thrombocytopenia, inflammation, and AKI in PUUV infection.
  • Hantavirus-neutralizing antibodies do not correlate with reduced disease severity in PUUV HFRS.

Conclusions:

  • Host genetic factors, particularly HLA alleles, significantly influence the clinical presentation of Puumala hantavirus infection.
  • While several factors are implicated, the precise mechanisms driving the extensive variation in PUUV disease severity remain largely elusive.
  • Plasma glucose concentration emerges as a potential biomarker for assessing PUUV infection severity.
Keywords:
HLAPuumala hantavirusbiomarkerhemorrhagic fever with renal syndromenephropathia epidemicaorthohantavirus

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