First complete-genome documentation of HIV-1 intersubtype superinfection with transmissions of diverse recombinants over time to five recipients

Gao, Yang; He, Shan; Tian, Wen; Li, Dan; An, Minghui; Zhao, Bin; Ding, Haibo; Xu, Junjie; Chu, Zhenxing; Shang, Hong; Han, Xiaoxu

doi:10.1371/journal.ppat.1009258

Cited by 11 publications

(16 citation statements)

References 58 publications

(26 reference statements)

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“…A total of 150 gag, 92 pol, and 252 nef cloned sequences were obtained and used for viral evolution analyses. The results showed that, in agreement with our previous studies (27), the patient was first infected with HIV-1 strain CRF01_AE, and then superinfected with a CRF07_BC strain. The latter accounted for 64.52% (20/ 31), 12.50% (3/24), and 8.70% (4/46) of the cloned sequences for the gag, pol, and nef genes at 300 dpi, respectively (Figure 2).…”

Section: Continuous Evolution Of Crf01_ae/ Crf07_bc Recombinants In T...supporting

confidence: 92%

“…Patient LNA819 was recruited from a previously described (26)(27)(28)(29) large-scale, prospective, high-risk, MSM cohort in Liaoning Province, China. Briefly, HIV-1-negative MSM were followed up every 8 weeks.…”

Section: Study Participantmentioning

confidence: 99%

“…The number of unique recombinant forms (URFs) of HIV-1 CRF01_AE/CRF07_BC was detected in patient LNA819 during the follow-up based on the recombination structure analysis of 3′ half genome sequences (27). Considering that Gag, Pol, and Nef protein-specific T-cell responses exert strong selective pressure on viral evolution, the gag, pol, and nef genes were amplified and sequenced at eight time points from 19 to 756 dpi.…”

Section: Continuous Evolution Of Crf01_ae/ Crf07_bc Recombinants In T...mentioning

confidence: 99%

“…We have previously shown that superinfection/coinfection is highly prevalent among Chinese men who have sex with men (MSM) with HIV and contributes to rapid disease progression (26). Importantly, there is recent, direct evidence to support that HIV recombinants were transmitted from a coinfected/superinfected donor (patient LNA819) to 5 putative recipients, with recombination structure analysis indicating that continuous evolution occurred in vivo under selection from the host (27). However, the influence of cellular immune pressure on recombination in patient LNA819 was unclear.…”

Section: Introductionmentioning

confidence: 99%

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HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection

et al. 2022

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A series of HIV-1 CRF01_AE/CRF07_BC recombinants were previously found to have emerged gradually in a superinfected patient (patient LNA819). However, the extent to which T-cell responses influenced the development of these recombinants after superinfection is unclear. In this study, we undertook a recombination structure analysis of the gag, pol, and nef genes from longitudinal samples of patient LNA819. A total of 9 pol and 5 nef CRF01_AE/CRF07_BC recombinants were detected. The quasispecies makeup and the composition of the pol and nef gene recombinants changed continuously, suggestive of continuous evolution in vivo. T-cell responses targeting peptides of the primary strain and the recombination regions were screened. The results showed that Pol-LY10, Pol-RY9, and Nef-GL9 were the immunodominant epitopes. Pol-LY10 overlapped with the recombination breakpoints in multiple recombinants. For the LY10 epitope, escape from T-cell responses was mediated by both recombination with a CRF07_BC insertion carrying the T467E/T472V variants and T467N/T472V mutations originating in the CRF01_AE strain. In pol recombinants R8 and R9, the recombination breakpoints were located ~23 amino acids upstream of the RY9 epitope. The appearance of new recombination breakpoints harboring a CRF07_BC insertion carrying a R984K variant was associated with escape from RY9-specific T-cell responses. Although the Nef-GL9 epitope was located either within or 10~11 amino acids downstream of the recombination breakpoints, no variant of this epitope was observed in the nef recombinants. Instead, a F85V mutation originating in the CRF01_AE strain was the main immune escape mechanism. Understanding the cellular immune pressure on recombination is critical for monitoring the new circulating recombinant forms of HIV and designing epitope-based vaccines. Vaccines targeting antigens that are less likely to escape immune pressure by recombination and/or mutation are likely to be of benefit to patients with HIV-1.

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Section: Continuous Evolution Of Crf01_ae/ Crf07_bc Recombinants In T...supporting

confidence: 92%

Section: Study Participantmentioning

confidence: 99%

Section: Continuous Evolution Of Crf01_ae/ Crf07_bc Recombinants In T...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection

et al. 2022

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“…SARS-CoV-2 posed a significant threat to human lives, and recent studies have reported the rapidly emerged variants and their impact on clinical severity and vaccine protection [7,9,19]. In this study, we aimed to detect whether the coinfection of Considering the rapidly emerged SARS-CoV-2 variants worldwide, we hypothesized that the coinfected variants in hosts would aggravate the clinical severity, increase the change of viral recombination, and posed a greater threat to us [20]. Moreover, the coinfection index can be applied to other viruses in hosts.…”

Section: Discussionmentioning

confidence: 99%

Both Simulation and Sequencing Data Reveal Multiple SARS-CoV-2 Variants Coinfection in COVID-19 Pandemic

Jiang

et al. 2021

Preprint

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SARS-CoV-2 is a single-stranded RNA betacoronavirus with a high mutation rate. The rapidly emerged SARS-CoV-2 variants could increase the transmissibility, aggravate the severity, and even fade the vaccine protection. Although the coinfections of SARS-CoV-2 with other respiratory pathogens have been reported, whether multiple SARS-CoV-2 variants coinfection exists remains controversial. This study collected 12,986 and 4,113 SARS-CoV-2 genomes from the GISAID database on May 11, 2020 (GISAID20May11) and April 1, 2021 (GISAID21Apr1), respectively. With the single-nucleotide variants (SNV) and network clique analysis, we constructed the single-nucleotide polymorphism (SNP) coexistence networks and noted the SNP number of the maximal clique as the coinfection index. The coinfection indices of GISAID20May11 and GISAID21Apr1 datasets were 16 and 34, respectively. Simulating the transmission routes and the mutation accumulations, we discovered the linear relationship between the coinfection index and the coinfected variant number. Based on the linear relationship, we deduced that the COVID-19 cases in the GISAID20May11 and GISAID21Apr1 datasets were coinfected with 2.20 and 3.42 SARS-CoV-2 variants on average. Additionally, we performed Nanopore sequencing on 42 COVID-19 patients to explore the virus mutational characteristics. We found the heterozygous SNPs in 41 COVID-19 cases, which support the coinfection of SARS-CoV-2 variants and challenge the accuracy of phylogenetic analysis. In conclusion, our findings reported the coinfection of SARS-CoV-2 variants in COVID-19 patients, demonstrated the increased coinfected variants number in the epidemic, and provided clues for the prolonged viral shedding and severe symptoms in some cases.

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Both simulation and sequencing data reveal coinfections with multiple SARS-CoV-2 variants in the COVID-19 pandemic

Jiang

et al. 2022

Computational and Structural Biotechnology Journal

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First complete-genome documentation of HIV-1 intersubtype superinfection with transmissions of diverse recombinants over time to five recipients

Cited by 11 publications

References 58 publications

HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection

HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection

Both Simulation and Sequencing Data Reveal Multiple SARS-CoV-2 Variants Coinfection in COVID-19 Pandemic

Both simulation and sequencing data reveal coinfections with multiple SARS-CoV-2 variants in the COVID-19 pandemic

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