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Drastic fitness loss in human immunodeficiency virus type 1 upon serial bottleneck events
E Yuste1, S Sánchez-Palomino, C Casado
1Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain.
Abstract:
Muller's ratchet predicts fitness losses in small populations of asexual organisms because of the irreversible accumulation of deleterious mutations and genetic drift. This effect should be enhanced if population bottlenecks intervene and fixation of mutations is not compensated by recombination. To study whether Muller's ratchet could operate in a retrovirus, 10 biological clones were derived from a human immunodeficiency virus type 1 (HIV-1) field isolate by MT-4 plaque assay. Each clone was subjected to 15 plaque-to-plaque passages. Surprisingly, genetic deterioration of viral clones was very drastic, and only 4 of the 10 initial clones were able to produce viable progeny after the serial plaque transfers. Two of the initial clones stopped forming plaques at passage 7, two others stopped at passage 13, and only four of the remaining six clones yielded infectious virus. Of these four, three displayed important fitness losses. Thus, despite virions carrying two copies of genomic RNA and the system displaying frequent recombination, HIV-1 manifested a drastic fitness loss as a result of an accentuation of Muller's ratchet effect.
Insights
Muller's ratchet, a genetic process, caused significant fitness loss in human immunodeficiency virus type 1 (HIV-1) populations. Despite recombination, HIV-1 showed drastic genetic deterioration, highlighting risks for small viral populations.
Area of Science:
- Virology
- Evolutionary Biology
- Genetics
Background:
- Muller's ratchet describes fitness decline in asexual populations due to irreversible accumulation of deleterious mutations.
- This process is exacerbated by population bottlenecks and lack of recombination.
- Retroviruses, like HIV-1, present a unique system to study Muller's ratchet due to their genetic characteristics.
Purpose of the Study:
- To investigate the potential operation of Muller's ratchet in human immunodeficiency virus type 1 (HIV-1).
- To assess the impact of serial passage on viral fitness and genetic stability in HIV-1.
Main Methods:
- Ten biological clones of HIV-1 were derived from a field isolate.
- Each clone underwent 15 serial plaque-to-plaque passages.
- Viral viability and plaque-forming ability were monitored throughout the passages.
Main Results:
- A drastic genetic deterioration was observed in the HIV-1 clones.
- Only 4 out of 10 initial clones produced viable progeny after serial transfers.
- Three of the four viable clones exhibited significant fitness losses, indicating Muller's ratchet effect.
Conclusions:
- HIV-1 demonstrated a pronounced Muller's ratchet effect, leading to substantial fitness loss.
- This occurred despite the presence of two genomic RNA copies and frequent recombination in virions.
- The findings suggest that Muller's ratchet can significantly impact retroviral populations, even with compensatory mechanisms.