Dynamics of haplotype frequency change in a CD8+TL epitope of simian immunodeficiency virus

Austin L. Hughes, Shelby O'Connor, Dawn M. Dudley, Benjamin Burwitz, Benjamin N. Bimber, David O'Connor

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Deep pyrosequencing of a CD8+TL epitope from the Tat protein of simian immunodeficiency virus (SIV) from four infected rhesus macaques carrying the restricting MHC allele (Mamu-A*01) for that epitope, revealed that natural selection favoring escape mutations led to an increase in the frequency of haplotypes in the epitope region that differed from the inoculum. After 20 weeks of infection, a new sequence haplotype in the epitope region had increased to a frequency greater than 50% in each of the four monkeys (range 57.9-98.9%); but the predominant haplotype was not the same in all four monkeys. Thus, even under strong selection favoring escape from CD8+TL recognition, the random nature of mutation itself is the primary factor affecting which escape mutation is likely to become predominant within an individual host. The relationship between the frequency of the inoculum haplotype in the epitope region and time post-infection approximated a simple hyperbola. On this assumption, the expected ratio of the frequencies at the inoculum at two times t1 and t2, fi(t2)/fi(t1), will be given by t1/t2. Because standard phylogenetic methods for reconstructing ancestral sequences failed to predict the inoculum sequence correctly, we used this relationship to predict the inoculum sequence with 100% accuracy, given data on haplotype frequencies at different time periods.

Original languageEnglish (US)
Pages (from-to)555-560
Number of pages6
JournalInfection, Genetics and Evolution
Volume10
Issue number4
DOIs
StatePublished - May 2010
Externally publishedYes

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
Haplotypes
epitopes
Epitopes
mutation
haplotypes
virus
inoculum
Mutation
Haplorhini
monkeys
natural selection
tat Gene Products
allele
Genetic Selection
phylogenetics
Macaca mulatta
Infection
protein

Keywords

  • Cytotoxic T lymphocyte
  • Escape mutation
  • Positive selection
  • Pyrosequencing
  • Simian immunodeficiency virus

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Molecular Biology
  • Microbiology
  • Infectious Diseases
  • Microbiology (medical)

Cite this

Dynamics of haplotype frequency change in a CD8+TL epitope of simian immunodeficiency virus. / Hughes, Austin L.; O'Connor, Shelby; Dudley, Dawn M.; Burwitz, Benjamin; Bimber, Benjamin N.; O'Connor, David.

In: Infection, Genetics and Evolution, Vol. 10, No. 4, 05.2010, p. 555-560.

Research output: Contribution to journalArticle

Hughes, Austin L. ; O'Connor, Shelby ; Dudley, Dawn M. ; Burwitz, Benjamin ; Bimber, Benjamin N. ; O'Connor, David. / Dynamics of haplotype frequency change in a CD8+TL epitope of simian immunodeficiency virus. In: Infection, Genetics and Evolution. 2010 ; Vol. 10, No. 4. pp. 555-560.
@article{dbb2f63cf7dd47879e8019c194f5d13f,
title = "Dynamics of haplotype frequency change in a CD8+TL epitope of simian immunodeficiency virus",
abstract = "Deep pyrosequencing of a CD8+TL epitope from the Tat protein of simian immunodeficiency virus (SIV) from four infected rhesus macaques carrying the restricting MHC allele (Mamu-A*01) for that epitope, revealed that natural selection favoring escape mutations led to an increase in the frequency of haplotypes in the epitope region that differed from the inoculum. After 20 weeks of infection, a new sequence haplotype in the epitope region had increased to a frequency greater than 50{\%} in each of the four monkeys (range 57.9-98.9{\%}); but the predominant haplotype was not the same in all four monkeys. Thus, even under strong selection favoring escape from CD8+TL recognition, the random nature of mutation itself is the primary factor affecting which escape mutation is likely to become predominant within an individual host. The relationship between the frequency of the inoculum haplotype in the epitope region and time post-infection approximated a simple hyperbola. On this assumption, the expected ratio of the frequencies at the inoculum at two times t1 and t2, fi(t2)/fi(t1), will be given by t1/t2. Because standard phylogenetic methods for reconstructing ancestral sequences failed to predict the inoculum sequence correctly, we used this relationship to predict the inoculum sequence with 100{\%} accuracy, given data on haplotype frequencies at different time periods.",
keywords = "Cytotoxic T lymphocyte, Escape mutation, Positive selection, Pyrosequencing, Simian immunodeficiency virus",
author = "Hughes, {Austin L.} and Shelby O'Connor and Dudley, {Dawn M.} and Benjamin Burwitz and Bimber, {Benjamin N.} and David O'Connor",
year = "2010",
month = "5",
doi = "10.1016/j.meegid.2010.02.001",
language = "English (US)",
volume = "10",
pages = "555--560",
journal = "Infection, Genetics and Evolution",
issn = "1567-1348",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Dynamics of haplotype frequency change in a CD8+TL epitope of simian immunodeficiency virus

AU - Hughes, Austin L.

AU - O'Connor, Shelby

AU - Dudley, Dawn M.

AU - Burwitz, Benjamin

AU - Bimber, Benjamin N.

AU - O'Connor, David

PY - 2010/5

Y1 - 2010/5

N2 - Deep pyrosequencing of a CD8+TL epitope from the Tat protein of simian immunodeficiency virus (SIV) from four infected rhesus macaques carrying the restricting MHC allele (Mamu-A*01) for that epitope, revealed that natural selection favoring escape mutations led to an increase in the frequency of haplotypes in the epitope region that differed from the inoculum. After 20 weeks of infection, a new sequence haplotype in the epitope region had increased to a frequency greater than 50% in each of the four monkeys (range 57.9-98.9%); but the predominant haplotype was not the same in all four monkeys. Thus, even under strong selection favoring escape from CD8+TL recognition, the random nature of mutation itself is the primary factor affecting which escape mutation is likely to become predominant within an individual host. The relationship between the frequency of the inoculum haplotype in the epitope region and time post-infection approximated a simple hyperbola. On this assumption, the expected ratio of the frequencies at the inoculum at two times t1 and t2, fi(t2)/fi(t1), will be given by t1/t2. Because standard phylogenetic methods for reconstructing ancestral sequences failed to predict the inoculum sequence correctly, we used this relationship to predict the inoculum sequence with 100% accuracy, given data on haplotype frequencies at different time periods.

AB - Deep pyrosequencing of a CD8+TL epitope from the Tat protein of simian immunodeficiency virus (SIV) from four infected rhesus macaques carrying the restricting MHC allele (Mamu-A*01) for that epitope, revealed that natural selection favoring escape mutations led to an increase in the frequency of haplotypes in the epitope region that differed from the inoculum. After 20 weeks of infection, a new sequence haplotype in the epitope region had increased to a frequency greater than 50% in each of the four monkeys (range 57.9-98.9%); but the predominant haplotype was not the same in all four monkeys. Thus, even under strong selection favoring escape from CD8+TL recognition, the random nature of mutation itself is the primary factor affecting which escape mutation is likely to become predominant within an individual host. The relationship between the frequency of the inoculum haplotype in the epitope region and time post-infection approximated a simple hyperbola. On this assumption, the expected ratio of the frequencies at the inoculum at two times t1 and t2, fi(t2)/fi(t1), will be given by t1/t2. Because standard phylogenetic methods for reconstructing ancestral sequences failed to predict the inoculum sequence correctly, we used this relationship to predict the inoculum sequence with 100% accuracy, given data on haplotype frequencies at different time periods.

KW - Cytotoxic T lymphocyte

KW - Escape mutation

KW - Positive selection

KW - Pyrosequencing

KW - Simian immunodeficiency virus

UR - http://www.scopus.com/inward/record.url?scp=77951978212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951978212&partnerID=8YFLogxK

U2 - 10.1016/j.meegid.2010.02.001

DO - 10.1016/j.meegid.2010.02.001

M3 - Article

C2 - 20149896

AN - SCOPUS:77951978212

VL - 10

SP - 555

EP - 560

JO - Infection, Genetics and Evolution

JF - Infection, Genetics and Evolution

SN - 1567-1348

IS - 4

ER -