Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST
ABSTRACT Many HIV prevention strategies are currently under consideration where it is highly informative to know the study participants’ times of infection. These can be estimated using viral sequence data sampled early in infection. However, there are several scenarios that, if not addressed, can s...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-04-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00324-20 |
| _version_ | 1819007153622482944 |
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| author | Elena E. Giorgi Hui Li Tanmoy Bhattacharya George M. Shaw Bette Korber |
| author_facet | Elena E. Giorgi Hui Li Tanmoy Bhattacharya George M. Shaw Bette Korber |
| author_sort | Elena E. Giorgi |
| collection | DOAJ |
| description | ABSTRACT Many HIV prevention strategies are currently under consideration where it is highly informative to know the study participants’ times of infection. These can be estimated using viral sequence data sampled early in infection. However, there are several scenarios that, if not addressed, can skew timing estimates. These include multiple transmitted/founder (TF) viruses, APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like)-mediated mutational enrichment, and recombination. Here, we suggest a pipeline to identify these problems and resolve the biases that they introduce. We then compare two modeling strategies to obtain timing estimates from sequence data. The first, Poisson Fitter (PF), is based on a Poisson model of random accumulation of mutations relative to the TF virus (or viruses) that established the infection. The second uses a coalescence-based phylogenetic strategy as implemented in BEAST. The comparison is based on timing predictions using plasma viral RNA (cDNA) sequence data from 28 simian-human immunodeficiency virus (SHIV)-infected animals for which the exact day of infection is known. In this particular setting, based on nucleotide sequences from samples obtained in early infection, the Poisson method yielded more accurate, more precise, and unbiased estimates for the time of infection than did the explored implementations of BEAST. IMPORTANCE The inference of the time of infection is a critical parameter in testing the efficacy of clinical interventions in protecting against HIV-1 infection. For example, in clinical trials evaluating the efficacy of passively delivered antibodies (Abs) for preventing infections, accurate time of infection data are essential for discerning levels of the Abs required to confer protection, given the natural Ab decay rate in the human body. In such trials, genetic sequences from early in the infection are regularly sampled from study participants, generally prior to immune selection, when the viral population is still expanding and genetic diversity is low. In this particular setting of early viral growth, the Poisson method is superior to the alternative approach based on coalescent methods. This approach can also be applied in human vaccine trials, where accurate estimates of infection times help ascertain if vaccine-elicited immune protection wanes over time. |
| first_indexed | 2024-12-21T00:20:03Z |
| format | Article |
| id | doaj.art-30d9bab6c88c43259eb13ceab14d43db |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-21T00:20:03Z |
| publishDate | 2020-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-30d9bab6c88c43259eb13ceab14d43db2022-12-21T19:22:07ZengAmerican Society for MicrobiologymBio2150-75112020-04-0111210.1128/mBio.00324-20Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEASTElena E. Giorgi0Hui Li1Tanmoy Bhattacharya2George M. Shaw3Bette Korber4Los Alamos National Laboratory, Los Alamos, New Mexico, USAPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USALos Alamos National Laboratory, Los Alamos, New Mexico, USAPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USALos Alamos National Laboratory, Los Alamos, New Mexico, USAABSTRACT Many HIV prevention strategies are currently under consideration where it is highly informative to know the study participants’ times of infection. These can be estimated using viral sequence data sampled early in infection. However, there are several scenarios that, if not addressed, can skew timing estimates. These include multiple transmitted/founder (TF) viruses, APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like)-mediated mutational enrichment, and recombination. Here, we suggest a pipeline to identify these problems and resolve the biases that they introduce. We then compare two modeling strategies to obtain timing estimates from sequence data. The first, Poisson Fitter (PF), is based on a Poisson model of random accumulation of mutations relative to the TF virus (or viruses) that established the infection. The second uses a coalescence-based phylogenetic strategy as implemented in BEAST. The comparison is based on timing predictions using plasma viral RNA (cDNA) sequence data from 28 simian-human immunodeficiency virus (SHIV)-infected animals for which the exact day of infection is known. In this particular setting, based on nucleotide sequences from samples obtained in early infection, the Poisson method yielded more accurate, more precise, and unbiased estimates for the time of infection than did the explored implementations of BEAST. IMPORTANCE The inference of the time of infection is a critical parameter in testing the efficacy of clinical interventions in protecting against HIV-1 infection. For example, in clinical trials evaluating the efficacy of passively delivered antibodies (Abs) for preventing infections, accurate time of infection data are essential for discerning levels of the Abs required to confer protection, given the natural Ab decay rate in the human body. In such trials, genetic sequences from early in the infection are regularly sampled from study participants, generally prior to immune selection, when the viral population is still expanding and genetic diversity is low. In this particular setting of early viral growth, the Poisson method is superior to the alternative approach based on coalescent methods. This approach can also be applied in human vaccine trials, where accurate estimates of infection times help ascertain if vaccine-elicited immune protection wanes over time.https://journals.asm.org/doi/10.1128/mBio.00324-20evolutionHIVSHIVtransmission |
| spellingShingle | Elena E. Giorgi Hui Li Tanmoy Bhattacharya George M. Shaw Bette Korber Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST mBio evolution HIV SHIV transmission |
| title | Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST |
| title_full | Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST |
| title_fullStr | Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST |
| title_full_unstemmed | Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST |
| title_short | Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST |
| title_sort | estimating the timing of early simian human immunodeficiency virus infections a comparison between poisson fitter and beast |
| topic | evolution HIV SHIV transmission |
| url | https://journals.asm.org/doi/10.1128/mBio.00324-20 |
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