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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
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Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
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Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2.

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Severely immunocompromised patients can shed viable SARS-CoV-2 for months, developing significant viral diversity within their bodies. This highlights the need for focused research on persistent infections and viral evolution in these vulnerable individuals.

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Area of Science:

  • Virology
  • Immunology
  • Genetics

Background:

  • Persistent infections with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are a concern, particularly in severely immunocompromised individuals.
  • The emergence of new SARS-CoV-2 variants, such as B.1.1.7, underscores the importance of understanding viral evolution during prolonged shedding.

Purpose of the Study:

  • To investigate the clinical profiles and viral characteristics associated with prolonged SARS-CoV-2 shedding in severely immunocompromised patients.
  • To analyze the intra-patient viral diversity and evolutionary dynamics in persistent SARS-CoV-2 infections.

Main Methods:

  • Whole-genome sequencing of sequential samples from three severely immunocompromised patients with prolonged SARS-CoV-2 shedding.
  • Analysis of single nucleotide polymorphisms (SNPs) to assess viral diversity and evolutionary rates.
  • Viral viability assessment through Ct values and cell culture recovery.

Main Results:

  • Two of three patients with lymphoma and prolonged shedding (2-6 months) died.
  • Extensive intra-patient SARS-CoV-2 diversity with 12 and 28 new SNPs observed in two patients, indicating ongoing replication.
  • Different evolutionary dynamics were observed, with rapid SNP fixation in one patient and slower emergence in another. Hyperimmune plasma administration appeared to slow viral evolution in one case.

Conclusions:

  • Severely immunocompromised patients can harbor viable SARS-CoV-2 with significant intra-patient diversity and distinct evolutionary patterns.
  • Understanding these persistent infections is crucial for managing viral evolution and developing targeted therapies.
  • Further research into the mechanisms driving prolonged shedding and viral adaptation in immunocompromised hosts is warranted.