2016
DOI: 10.1002/jmv.24610
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Increased replication capacity following evolution of PYxE insertion in Gag‐p6 is associated with enhanced virulence in HIV‐1 subtype C from East Africa

Abstract: This is the first evidence of polymerase independent increased virulence and RC in HIV-1C following PYxE-insertion that is associated with suboptimal CD4 T-cell gain following therapy initiation. J. Med. Virol. 89:106-111, 2017. © 2016 Wiley Periodicals, Inc.

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Cited by 12 publications
(18 citation statements)
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“…This correlation suggests that HIV-1C strains with a PYxE insertion have a growth advantage compared to wild type HIV-1C. This is also in line with our earlier study that HIV-1C PYQEi viruses are more replication competent as well as more pathogenic (17).…”
Section: Resultssupporting
confidence: 89%
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“…This correlation suggests that HIV-1C strains with a PYxE insertion have a growth advantage compared to wild type HIV-1C. This is also in line with our earlier study that HIV-1C PYQEi viruses are more replication competent as well as more pathogenic (17).…”
Section: Resultssupporting
confidence: 89%
“…Furthermore, the insertion appears more frequent among patients on antiretroviral therapy, e.g., ritonavir-boosted protease inhibitors (PI), compared to therapy naïve patients in India, and more frequent in therapy-failure patients in South Africa (15, 16). Moreover, lower pre-therapy CD4 + T cell counts, higher plasma viral loads, and reduced increase in CD4 + T cell counts were noted to be associated with PYxE insertion in HIV-1C patients compared to patients with wild type HIV-1C from East Africa (17). Furthermore, we observed that increased replication fitness in PYQE inserted HIV-1C viruses was polymerase independent (17).…”
Section: Introductionmentioning
confidence: 99%
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“…It is also of interest that an unusual mutant with deletion at residues 482 and 483, shown to disrupt Alix binding (68), was previously associated with nonprogressive HIV-1 infection (69), indicating that the ability to bind Alix may influence disease progression. Furthermore, it was recently described that a PYxE insertion (at the same position as the LY motif) in some East African subtype C isolates enhanced the replication capacity and virulence of these isolates compared to subtype C isolates without the insertion (70).…”
Section: Discussionmentioning
confidence: 99%
“…For example, it has been hypothesized that HIV-1 subtype C isolates, which comprise more than >50% of infections worldwide (Hemelaar, 2012), may be inherently more transmissible - possibly because of subtype-specific motifs within Env-gp120 that modulate interactions with host cell entry receptors (Walter et al, 2009) - though this remains controversial (Kahle et al, 2014). Subtype-specific differences in HIV-1 entry efficiency (Marozsan et al, 2005), replication capacity (Aralaguppe et al, 2016; Konings et al, 2006), and the function of viral accessory proteins Vif (Binka et al, 2012; Iwabu et al, 2010) and Nef (Mann et al, 2013) have also been described. Methods to assess the function of other HIV-1 proteins encoded by natural sequences are thus warranted.…”
Section: Introductionmentioning
confidence: 99%