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Published on: August 31, 2014
Genetic drift of parvovirus B19 is found in AIDS patients with persistent B19 infection
Chien-Ching Hung1, Wang-Hwei Sheng, Kuang-Lun Lee
1Department of Internal Medicine, Section of Infectious Disease, National Taiwan University Hospital, Taipei, Taiwan.
Abstract:
It is generally thought that parvovirus B19 is stable genetically. Consistently, genetic drift has not been found in patients with persistent B19 infection. In this report, longitudinal genetic changes in NS1 and VP1 gene of B19 isolates from three AIDS patients with persistent B19 infection were studied. One of the three patients was not treated with highly active anti-retroviral therapy (HAART). B19 viral DNA from these patients was amplified by polymerase chain reaction (PCR) and then sequenced directly. A single genetic change was found in the B19 isolate obtained from the patient not treated with HAART on Day 10 after intravenous immunoglobulin (IVIG) treatment. The nucleotide sequences of B19 isolated from this patient, then remained unchanged over a period of 11 months. Analysis of NS1 clones derived from his longitudinal viral isolates showed the existence of quasi-species but genetic drift was not found. One of the other two patients treated with HAART experienced treatment failure; he was later treated with mega-HAART. In contrast to the genetic stability of B19 isolates from the patient not treated with HAART, multiple genetic changes were discovered in the viral isolates from the two other patients after HAART and mega-HAART, respectively. Through analysis of B19 clones, the frequency of clones containing these mutations confirmed the genetic drift. Nucleotide substitutions seen in VP2 gene of isolates with genetic drift from both patients were all non-conserved, suggesting that they are positively selected.
Insights
Parvovirus B19 is generally stable, but persistent infections in AIDS patients show genetic changes. Highly active anti-retroviral therapy (HAART) correlates with parvovirus B19 genetic drift.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Parvovirus B19 is typically considered genetically stable, with no prior evidence of genetic drift in persistent infections.
- Persistent parvovirus B19 infection is a concern in immunocompromised individuals, such as those with Acquired Immunodeficiency Syndrome (AIDS).
Observation:
- This study investigated longitudinal genetic changes in parvovirus B19 NS1 and VP1 genes from three AIDS patients with persistent B19 infection.
- One patient received no highly active anti-retroviral therapy (HAART), while two others received HAART, with one experiencing treatment failure and subsequent mega-HAART.
- B19 viral DNA was amplified using polymerase chain reaction (PCR) and directly sequenced.
Findings:
- A single genetic change was observed in the B19 isolate from the untreated patient post-intravenous immunoglobulin (IVIG) treatment, with subsequent stability over 11 months.
- Analysis of NS1 clones revealed quasi-species but no genetic drift in the untreated patient.
- In contrast, multiple genetic changes and confirmed genetic drift were observed in B19 isolates from the two HAART-treated patients, particularly after HAART and mega-HAART interventions.
- Non-conserved nucleotide substitutions in the VP2 gene of drifting isolates suggest positive selection.
Implications:
- The findings challenge the notion of parvovirus B19's universal genetic stability, especially in the context of persistent infections and specific therapeutic interventions.
- Highly active anti-retroviral therapy (HAART) and related treatments may influence the genetic evolution of parvovirus B19 in AIDS patients.
- Understanding these genetic dynamics is crucial for managing persistent parvovirus B19 infections and developing effective treatment strategies in immunocompromised populations.
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