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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.
Abstract:
The clinical outcome of Puumala hantavirus (PUUV) infection shows extensive variation, ranging from inapparent subclinical infection (70-80%) to severe hemorrhagic fever with renal syndrome (HFRS), with about 0.1% of cases being fatal. Most hospitalized patients experience acute kidney injury (AKI), histologically known as acute hemorrhagic tubulointerstitial nephritis. Why this variation? There is no evidence that there would be more virulent and less virulent variants infecting humans, although this has not been extensively studied. Individuals with the human leukocyte antigen (HLA) alleles B*08 and DRB1*0301 are likely to have a severe form of the PUUV infection, and those with B*27 are likely to have a benign clinical course. Other genetic factors, related to the tumor necrosis factor (TNF) gene and the C4A component of the complement system, may be involved. Various autoimmune phenomena and Epstein-Barr virus infection are associated with PUUV infection, but hantavirus-neutralizing antibodies are not associated with lower disease severity in PUUV HFRS. Wide individual differences occur in ocular and central nervous system (CNS) manifestations and in the long-term consequences of nephropathia epidemica (NE). Numerous biomarkers have been detected, and some are clinically used to assess and predict the severity of PUUV infection. A new addition is the plasma glucose concentration associated with the severity of both capillary leakage, thrombocytopenia, inflammation, and AKI in PUUV infection. Our question, "Why this variation?" remains largely unanswered.
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.
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