High Rate of Recombination throughout the Human Immunodeficiency Virus Type 1 Genome

Jetzt, Amanda E.; Yu, Hong; Klarmann, George J.; Ron, Yacov; Preston, Bradley D.; Dougherty, Joseph P.

doi:10.1128/jvi.74.3.1234-1240.2000

Cited by 331 publications

(297 citation statements)

References 48 publications

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“…An extrapolation of this estimate of 0.13 recombination events to the full-length genome (nearly 10,000 nt long in contrast to the 400-nt region used here) predicts 3.25 recombination events per each infection cycle. This value is in agreement with the estimate of three recombination events per infectious cycle made by Jetzt and colleagues (16).…”

Section: Recombination In Hiv-1 After a Single Cycle Of Infection-wesupporting

confidence: 82%

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The Structure of HIV-1 Genomic RNA in the gp120 Gene Determines a Recombination Hot Spot in Vivo

Galetto¹,

Moumen²,

Giacomoni³

et al. 2004

Journal of Biological Chemistry

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By frequently rearranging large regions of the genome, genetic recombination is a major determinant in the plasticity of the human immunodeficiency virus type I (HIV-1) population. In retroviruses, recombination mostly occurs by template switching during reverse transcription. The generation of retroviral vectors provides a means to study this process after a single cycle of infection of cells in culture. Using HIV-1-derived vectors, we present here the first characterization and estimate of the strength of a recombination hot spot in HIV-1 in vivo. In the hot spot region, located within the C2 portion of the gp120 envelope gene, the rate of recombination is up to ten times higher than in the surrounding regions. The hot region corresponds to a previously identified RNA hairpin structure. Although recombination breakpoints in vivo cluster in the top portion of the hairpin, the bias for template switching in this same region appears less marked in a cell-free system. By modulating the stability of this hairpin we were able to affect the local recombination rate both in vitro and in infected cells, indicating that the local folding of the genomic RNA is a major parameter in the recombination process. This characterization of reverse transcription products generated after a single cycle of infection provides insights in the understanding of the mechanism of recombination in vivo and suggests that specific regions of the genome might be prompted to yield different rates of evolution due to the presence of circumscribed recombination hot spots.

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Section: Recombination In Hiv-1 After a Single Cycle Of Infection-wesupporting

confidence: 82%

“…Indeed, ex vivo experiments in HeLa CD4 ϩ -infected cells estimated that three events of template switching occur, on average, per replication cycle (16). Furthermore, it has recently been shown that the recombination rates are influenced by the type of cell infected, with the highest rates observed in macrophages (17).…”

mentioning

confidence: 99%

The Structure of HIV-1 Genomic RNA in the gp120 Gene Determines a Recombination Hot Spot in Vivo

Galetto¹,

Moumen²,

Giacomoni³

et al. 2004

Journal of Biological Chemistry

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“…Prior studies quantifying HIV-1 RT-strand transfer frequencies across the HIV-1 genome have been conducted only during infection of HeLa-CD4 fibroblastic cells and have demonstrated a minimal average of three to four RSTE per virus per round of replication (19)(20)(21). Because the intracellular environments of diverse cell types vary, we sought to determine the frequency of RT-strand transfer directly during HIV-1 infection of a natural target of HIV-1 infection.…”

Section: Resultsmentioning

confidence: 99%

Dynamics of HIV-1 recombination in its natural target cells

Levy

Aldrovandi

Kutsch

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

407

513

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Genetic recombination is believed to assist HIV-1 diversification and escape from host immunity and antiviral therapies, yet this process remains largely unexamined within the natural target-cell populations. We developed a method for measuring HIV-1 recombination directly that employs reporter viruses bearing functional enhanced yellow fluorescent protein (YFP) and enhanced cyan fluorescent protein (CFP) genes in which recombination produces a modified GFP gene and GFP fluorescence in the infected cells. These reporter viruses allow simultaneous quantification of the dynamics of HIV-1 infection, coinfection, and recombination in cell culture and in animal models by flow-cytometric analysis. Multiround infection assays revealed that productive cellular coinfection was subject to little functional inhibition. As a result, generation of recombinants proceeded according to the square of the infection rate during HIV-1 replication in T lymphocytes and within human thymic grafts in severe combined immunodeficient (SCID)-hu (Thy/Liv) mice. These results suggest that increases in viral load may confer a compounding risk of virus escape by means of recombinational diversification. A single round of replication in T lymphocytes in culture generated an average of nine recombination events per virus, and infection of macrophages led to ≈30 crossover events, making HIV-1 up to an order of magnitude more recombinogenic than recognized previously and demonstrating that the infected cell exerts a profound influence on the frequency of recombination

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“…There is no phylogenetic evidence of recombination by analyzing 54 full-length HCV isolates retrieved from the GenBank database. Recombination is a common phenomenon for viruses with an RNA genome, such as human immunodeficiency virus 39,40 and influenza virus. 41 There is also phylogenetic evidence of recombination for dengue virus 42 and hepatitis G virus, 43 both of which belong to the Flaviviridae as the HCV.…”

Section: Discussionmentioning

confidence: 99%

Liver Transplantation With Hepatitis C Virus–Infected Graft: Interaction Between Donor and Recipient Viral Strains

Fan

Lang

et al. 2003

Hepatology

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Superinfection of different viral strains within a single host provides an opportunity for studying host-virus and virus-virus interactions, including viral interference and genetic recombination, which cannot be studied in infections with single viral strains. Hepatitis C virus (HCV) is a positive single-strand RNA virus that establishes persistent infection in as many as 85% of infected individuals. However, there are few reports regarding coinfection or superinfection of HCV. Because of the lack of tissue culture systems and small animal models supporting efficient HCV replication, we explored these issues in the setting of liver transplantation where both recipient and donor were infected with different HCV strains and therefore represent a distinct model for HCV superinfection. Serial serum samples collected at multiple time points were obtained from 6 HCV-positive liver donor/recipient pairs from the National Institute of Diabetes and Digestive and Kidney Diseases liver transplantation database. At each time point, HCV genotype was determined by both restriction fragment length polymorphism analysis and phylogenetic analysis. Furthermore, we selectively sequenced 3 full-length HCV isolates at the earliest time points after liver transplantation, including both 5 and 3 ends. Detailed genetic analyses showed that only one strain of HCV could be identified at each time point in all 6 cases. Recipient HCV strains took over in 3 cases, whereas donor HCV strains dominated after liver transplantation in the remaining 3 cases. In conclusion, in all 6 cases studied, there was no genetic recombination detected among HCV quasispecies or between donor and recipient HCV strains. (HEPATOLOGY 2003;38: 25-33.)H epatitis C virus (HCV), a single-strand, positive RNA virus, has been well documented as the major etiologic agent responsible for most posttransfusional and community-acquired hepatitis. 1 HCVrelated liver disease is now a leading cause for liver transplantation in the United States. One striking characteristic of HCV infection is its high chronicity rate; that is, it easily establishes persistent infection in up to 85% of infected individuals and causes a wide spectrum of clinical profiles. The high chronicity rate of HCV may be partially attributed to its great genetic variability, which favors its rapid adaptation to a given biological environment. HCV may be divided into at least 6 major genotypes and more than 30 subtypes according to the phylogenies of available HCV sequences. 2 Moreover, even in patients infected with a single HCV subtype, HCV circulates as a group of variants with up to 10% nucleotide sequence difference, termed quasispecies. [3][4][5][6][7] Superinfection with different viral strains within a single host is a useful model for studying host-virus and virus-virus interactions. In HCV, perhaps due to the lack of protective immunity, 8 superinfection by different HCV isolates in patients with chronic HCV is clinically observed, in particular in individuals at very high risk for infection, suc...

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High Rate of Recombination throughout the Human Immunodeficiency Virus Type 1 Genome

Cited by 331 publications

References 48 publications

The Structure of HIV-1 Genomic RNA in the gp120 Gene Determines a Recombination Hot Spot in Vivo

The Structure of HIV-1 Genomic RNA in the gp120 Gene Determines a Recombination Hot Spot in Vivo

Dynamics of HIV-1 recombination in its natural target cells

Liver Transplantation With Hepatitis C Virus–Infected Graft: Interaction Between Donor and Recipient Viral Strains

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