Retroviral recombination in vivo

Viral replication patterns and genetic structure of simian immunodeficiency virus (SIV) populations in rhesus macaques after simultaneous or sequential intravaginal inoculation with SIVmac239Δvpx/Δvpr and SIVmac239Δnef

Eun Young Kim, Marc Busch, Kristina Abel, Linda Fritts, Patty Bustamante, Jenny Stanton, Ding Lu, Samuel Wu, Jenny Glowczwskie, Tracy Rourke, Derek Bogdan, Mike Piatak, Jeffrey D. Lifson, Ronald Charles Desrosiers, Steven Wolinsky, Christopher J. Miller

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

To characterize the occurrence, frequency, and kinetics of retroviral recombination in vivo, we intravaginally inoculated rhesus macaques, either simultaneously or sequentially, with attenuated simian immunodeficiency virus (SIV) strains having complementary deletions in their accessory genes and various degrees of replication impairment. In monkeys inoculated simultaneously with SIVmac239Δvpx/Δvpr and SIVmac239Δnef, recombinant wild-type (wt) virus and wild-type levels of plasma viral RNA (vRNA) were detected in blood by 2 weeks postinoculation. In monkeys inoculated first with SIVmac239Δvpx/Δvpr and then with SIVmac239Δnef, recombination occurred but was associated with lower plasma vRNA levels than plasma vRNA levels seen for monkeys inoculated intravaginally with wt SIVmac239. In one monkey, recombination occurred 6 weeks after the challenge with SIVmac239Δnef when plasma SIVmac239Δvpx/Δvpr RNA levels were undetectable. In monkeys inoculated first with the more highly replicating strain, SIVmac239Δnef, and then with SIVmac239Δvpx/ Δvpr, wild-type recombinant virus was not detected in blood or tissues. Instead, a virus that had repaired the deletion in the nef gene by a compensatory mutation was found in one animal. Overall, recombinant SIV was eventually found in four of six animals intravaginally inoculated with the two SIVmac239 deletion mutants. These findings show that recombination can occur readily in vivo after mucosal SIV exposure and thus contributes to the generation of viral genetic diversity and enhancement of viral fitness.

Original languageEnglish (US)
Pages (from-to)4886-4895
Number of pages10
JournalJournal of Virology
Volume79
Issue number8
DOIs
StatePublished - Apr 2005
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Genetic Structures
virus replication
Macaca mulatta
Genetic Recombination
Haplorhini
monkeys
Viral RNA
RNA
Population
Viruses
viruses
Genetic Enhancement
nef Genes
microbial genetics
gene deletion
blood
animals
mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Retroviral recombination in vivo : Viral replication patterns and genetic structure of simian immunodeficiency virus (SIV) populations in rhesus macaques after simultaneous or sequential intravaginal inoculation with SIVmac239Δvpx/Δvpr and SIVmac239Δnef. / Kim, Eun Young; Busch, Marc; Abel, Kristina; Fritts, Linda; Bustamante, Patty; Stanton, Jenny; Lu, Ding; Wu, Samuel; Glowczwskie, Jenny; Rourke, Tracy; Bogdan, Derek; Piatak, Mike; Lifson, Jeffrey D.; Desrosiers, Ronald Charles; Wolinsky, Steven; Miller, Christopher J.

In: Journal of Virology, Vol. 79, No. 8, 04.2005, p. 4886-4895.

Research output: Contribution to journalArticle

Kim, Eun Young ; Busch, Marc ; Abel, Kristina ; Fritts, Linda ; Bustamante, Patty ; Stanton, Jenny ; Lu, Ding ; Wu, Samuel ; Glowczwskie, Jenny ; Rourke, Tracy ; Bogdan, Derek ; Piatak, Mike ; Lifson, Jeffrey D. ; Desrosiers, Ronald Charles ; Wolinsky, Steven ; Miller, Christopher J. / Retroviral recombination in vivo : Viral replication patterns and genetic structure of simian immunodeficiency virus (SIV) populations in rhesus macaques after simultaneous or sequential intravaginal inoculation with SIVmac239Δvpx/Δvpr and SIVmac239Δnef. In: Journal of Virology. 2005 ; Vol. 79, No. 8. pp. 4886-4895.
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abstract = "To characterize the occurrence, frequency, and kinetics of retroviral recombination in vivo, we intravaginally inoculated rhesus macaques, either simultaneously or sequentially, with attenuated simian immunodeficiency virus (SIV) strains having complementary deletions in their accessory genes and various degrees of replication impairment. In monkeys inoculated simultaneously with SIVmac239Δvpx/Δvpr and SIVmac239Δnef, recombinant wild-type (wt) virus and wild-type levels of plasma viral RNA (vRNA) were detected in blood by 2 weeks postinoculation. In monkeys inoculated first with SIVmac239Δvpx/Δvpr and then with SIVmac239Δnef, recombination occurred but was associated with lower plasma vRNA levels than plasma vRNA levels seen for monkeys inoculated intravaginally with wt SIVmac239. In one monkey, recombination occurred 6 weeks after the challenge with SIVmac239Δnef when plasma SIVmac239Δvpx/Δvpr RNA levels were undetectable. In monkeys inoculated first with the more highly replicating strain, SIVmac239Δnef, and then with SIVmac239Δvpx/ Δvpr, wild-type recombinant virus was not detected in blood or tissues. Instead, a virus that had repaired the deletion in the nef gene by a compensatory mutation was found in one animal. Overall, recombinant SIV was eventually found in four of six animals intravaginally inoculated with the two SIVmac239 deletion mutants. These findings show that recombination can occur readily in vivo after mucosal SIV exposure and thus contributes to the generation of viral genetic diversity and enhancement of viral fitness.",
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T2 - Viral replication patterns and genetic structure of simian immunodeficiency virus (SIV) populations in rhesus macaques after simultaneous or sequential intravaginal inoculation with SIVmac239Δvpx/Δvpr and SIVmac239Δnef

AU - Kim, Eun Young

AU - Busch, Marc

AU - Abel, Kristina

AU - Fritts, Linda

AU - Bustamante, Patty

AU - Stanton, Jenny

AU - Lu, Ding

AU - Wu, Samuel

AU - Glowczwskie, Jenny

AU - Rourke, Tracy

AU - Bogdan, Derek

AU - Piatak, Mike

AU - Lifson, Jeffrey D.

AU - Desrosiers, Ronald Charles

AU - Wolinsky, Steven

AU - Miller, Christopher J.

PY - 2005/4

Y1 - 2005/4

N2 - To characterize the occurrence, frequency, and kinetics of retroviral recombination in vivo, we intravaginally inoculated rhesus macaques, either simultaneously or sequentially, with attenuated simian immunodeficiency virus (SIV) strains having complementary deletions in their accessory genes and various degrees of replication impairment. In monkeys inoculated simultaneously with SIVmac239Δvpx/Δvpr and SIVmac239Δnef, recombinant wild-type (wt) virus and wild-type levels of plasma viral RNA (vRNA) were detected in blood by 2 weeks postinoculation. In monkeys inoculated first with SIVmac239Δvpx/Δvpr and then with SIVmac239Δnef, recombination occurred but was associated with lower plasma vRNA levels than plasma vRNA levels seen for monkeys inoculated intravaginally with wt SIVmac239. In one monkey, recombination occurred 6 weeks after the challenge with SIVmac239Δnef when plasma SIVmac239Δvpx/Δvpr RNA levels were undetectable. In monkeys inoculated first with the more highly replicating strain, SIVmac239Δnef, and then with SIVmac239Δvpx/ Δvpr, wild-type recombinant virus was not detected in blood or tissues. Instead, a virus that had repaired the deletion in the nef gene by a compensatory mutation was found in one animal. Overall, recombinant SIV was eventually found in four of six animals intravaginally inoculated with the two SIVmac239 deletion mutants. These findings show that recombination can occur readily in vivo after mucosal SIV exposure and thus contributes to the generation of viral genetic diversity and enhancement of viral fitness.

AB - To characterize the occurrence, frequency, and kinetics of retroviral recombination in vivo, we intravaginally inoculated rhesus macaques, either simultaneously or sequentially, with attenuated simian immunodeficiency virus (SIV) strains having complementary deletions in their accessory genes and various degrees of replication impairment. In monkeys inoculated simultaneously with SIVmac239Δvpx/Δvpr and SIVmac239Δnef, recombinant wild-type (wt) virus and wild-type levels of plasma viral RNA (vRNA) were detected in blood by 2 weeks postinoculation. In monkeys inoculated first with SIVmac239Δvpx/Δvpr and then with SIVmac239Δnef, recombination occurred but was associated with lower plasma vRNA levels than plasma vRNA levels seen for monkeys inoculated intravaginally with wt SIVmac239. In one monkey, recombination occurred 6 weeks after the challenge with SIVmac239Δnef when plasma SIVmac239Δvpx/Δvpr RNA levels were undetectable. In monkeys inoculated first with the more highly replicating strain, SIVmac239Δnef, and then with SIVmac239Δvpx/ Δvpr, wild-type recombinant virus was not detected in blood or tissues. Instead, a virus that had repaired the deletion in the nef gene by a compensatory mutation was found in one animal. Overall, recombinant SIV was eventually found in four of six animals intravaginally inoculated with the two SIVmac239 deletion mutants. These findings show that recombination can occur readily in vivo after mucosal SIV exposure and thus contributes to the generation of viral genetic diversity and enhancement of viral fitness.

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