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Intrinsic and extrinsic factors affecting the evolution of virulence in the HIV-associated opportunistic human fungal

Yuanyuan Wang1, Yiwu Yu2,3, Jihong Liu1

  • 1Joint Laboratory for Biomedical Research and Pharmaceutical Innovation, Unit of Pathogenic Fungal Infection & Host Immunity, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.

Virulence
|August 14, 2025
PubMed

Insights

Genetic and environmental factors influence Cryptococcus neoformans virulence, with isolates from HIV-uninfected individuals showing enhanced traits. Host immunity and specific gene variations, like CDA3 and GPD1, are key to understanding this fungal pathogen.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Genetics

Background:

  • Cryptococcus neoformans is a major cause of mortality in immunocompromised individuals.
  • Understanding genotype-phenotype correlations in C. neoformans is crucial for explaining virulence.
  • The impact of genetic and environmental variability on C. neoformans virulence remains unclear.

Purpose of the Study:

  • To investigate the influence of genetic and environmental factors on C. neoformans virulence.
  • To analyze genotype-phenotype correlations in Chinese C. neoformans isolates.
  • To identify genetic variations associated with host-specific virulence.

Main Methods:

  • Multilocus sequence typing (MLST) of 105 C. neoformans isolates.
  • Phenotypic analysis of virulence traits (capsule, melanin, CSF survival, phagocytosis).
  • Whole-genome sequencing and genome-wide association studies (GWAS).

Main Results:

  • Sequence type 5 predominated in clinical isolates; genotypic diversity was higher in non-HIV and environmental isolates.
  • Isolates from HIV-uninfected individuals showed enhanced virulence traits and higher mortality in models.
  • Variations in carbohydrate metabolism genes (e.g., CDA3, GPD1) correlated with host-specific virulence.

Conclusions:

  • Genetic and environmental factors significantly shape C. neoformans virulence.
  • Host immunity, indicated by CD4+ T cell counts, plays a critical role in modulating virulence.
  • Specific gene variations contribute to host-specific evolution of C. neoformans virulence.
Keywords:
Cryptococcus neoformansenvironmental factorsgenetic variantsgenotype-phenotype correlationvirulence

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