Genetic Signatures of HIV-1 Envelope-mediated Bystander Apoptosis

Joshi, Anjali; Lee, Raphael Tze Chuen; Mohl, Jonathon E.; Sedano, Melina J.; Khong, Wei Xin; Ng, Oon Tek; Maurer‐Stroh, Sebastian; Garg, Himanshu

doi:10.1074/jbc.m113.514018

Cited by 15 publications

(30 citation statements)

References 87 publications

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“…The role of PNGS in viral tropism as well as sensitivity to neutralizing antibodies is well established (McMichael et al, 2010; Rong et al, 2009; Wei et al, 2003). Moreover, it is well studied that subtype B HIV seems to be highly sensitive to broadly neutralizing antibodies from our studies and others (Binley et al, 2004; Joshi et al, 2014). One could hence anticipate that increase in PNGS in subtype B is a consequence of selection against neutralizing antibodies.…”

Section: Discussionsupporting

confidence: 63%

“…It is worth noting here that while genotypic and phenotypic differences in AE and B subtype Envs correlates with CD4 decline, this correlation does not necessary mean causation. Although Env glycoprotein is a major determinant of HIV pathogenesis, (Garg et al, 2011; Garg et al, 2012; Joshi et al, 2014; Joshi et al, 2011) further studies will be needed including those with full length viruses derived from these Envs to determine the role of Env variants in AE versus B subtype pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

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HIV-1 subtype CRF01_AE and B differ in utilization of low levels of CCR5, Maraviroc susceptibility and potential N-glycosylation sites

et al. 2017

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HIV subtypes not only predominate in different geographical regions but also differ in key phenotypic characteristics. To determine if genotypic and/or phenotypic differences in the Envelope (Env) glycoprotein can explain subtype related differences, we cloned 37 full length Envs from Subtype B and AE HIV infected individuals from Singapore. Our data demonstrates that CRF01_AE Envs have lower Potential N Glycosylation Sites and higher risk of X4 development. Phenotypically, CRF01_AE were less infectious than subtype B Envs in cells expressing low levels of CCR5. Moreover, the Maraviroc IC50 was higher for subtype B Envs and correlated with infectivity in low CCR5 expressing cells as well as PNGS. Specifically, the glycosylation site N301 in the V3 loop was seen less frequently in AE subtype and CXCR4 topic viruses. CRF01_AE differs from B subtype in terms of CCR5 usage and Maraviroc susceptibility which may have implications for HIV pathogenesis and virus evolution.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

HIV-1 subtype CRF01_AE and B differ in utilization of low levels of CCR5, Maraviroc susceptibility and potential N-glycosylation sites

et al. 2017

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“…Moreover, the envelope proteins of several other RNA viruses, including human immunodeficiency virus, avian leukosis-sarcoma virus, Langat flavivirus, and Sindbis virus envelope, are known to induce apoptosis [13][14][15][16]. Based on these observations, we hypothesized that the DTMUV E protein may be important for DTMUV-induced apoptosis and examined whether DTMUV E protein induced cell apoptosis by transfecting pCDNA-E into DEF cells.…”

Section: Discussionmentioning

confidence: 99%

Duck tembusu virus and its envelope protein induce programmed cell death

Shaozhou

Zhang

et al. 2015

Virus Genes

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The cytopathic effect produced in cells infected with duck tembusu virus (DTMUV) suggests that this emerging virus may induce apoptosis in primary cultures of duck embryo fibroblasts (DEF). Here, we present evidence that DTMUV infection of cultured cells activates apoptosis and that the ability of DTMUV to induce apoptosis is not restricted to cell type because DTMUV-induced apoptosis in duck and mammalian host cells. We further investigated which viral components induce apoptosis in DTMUV-infected host cells. The major envelope glycoprotein (E) was investigated for its apoptotic activities in expressed cells. Transient expression of the E protein alone triggered apoptosis in DEF, Vero, and BHK cells. Expression of the E protein resulted in activation of caspase-3-like proteases in cultured cells. These results indicate that infection of cells with DTMUV or expression of DTMUV E protein alone induces apoptosis, providing the basis for future to define the molecules that play key roles in the fate of DTMUV-infected cells.

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“…We reasoned that this might have been caused by premature apoptosis of the packaging cells due to high levels of gp140. 29 We inserted the gp140 expression cassette into an E1-deleted viral molecular clone that contained the E3 domain. The rescued vector and target genome was initially changeable, however on subsequent passages remained stable.…”

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confidence: 99%

A PartialE3Deletion in Replication-Defective Adenoviral Vectors Allows for Stable Expression of Potentially Toxic Transgene Products

Haut

Gill

Kurupati

et al. 2016

Human Gene Therapy Methods

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Adenovirus (Ad) is used extensively for construction of viral vectors, most commonly with deletion in its E1 and/or E3 genomic regions. Previously, our attempts to insert envelope proteins (Env) of HIV-1 into such vectors based on chimpanzee-derived Ad (AdC) viruses were thwarted. Here, we describe that genetic instability of an E1-and E3-deleted AdC vector of serotype C6 expressing Env of HIV-1 can be overcome by reinsertion of E3 sequences with anti-apoptotic activities. This partial E3 deletion presumably delays premature death of HEK-293 packaging cell lines due to Env-induced cell apoptosis. The same partial E3 deletion also allows for the generation of stable glycoprotein 140 (gp140)-and gp160-expressing Ad vectors based on AdC7, a distinct AdC serotype. Env-expressing AdC vectors containing the partial E3 deletion are genetically stable upon serial cell culture passaging, produce yields comparable to those of other AdC vectors, and induce transgene product-specific antibody responses in mice. A partial E3 deletion thereby allows expansion of the repertoire of transgenes that can be expressed by Ad vectors.Keywords: HIV-1, vaccine, genetic stability, immune responses INTRODUCTION REPLICATION-DEFECTIVE ADENOVIRUS (Ad) vectors efficiently deliver transgenes to multiple cell types. 1,2 They trigger a potent inflammatory response, 3,4 which initiates adaptive immune responses to the transgene product and the antigens of the Ad vector. 5 This has led to the development of different Ad serotypes as vaccine carriers for a plethora of antigens derived from viruses, 6-10 bacteria, 11,12 parasites, 13,14 or tumor cells, [15][16][17] which have consistently induced potent and sustained B and T cell responses to the transgene products.In most Ad vaccine vectors, the E1 and E3 domains are deleted from the genome. The E1 deletion renders Ad vectors replication defective and reduces synthesis of other Ad antigens. E3 encodes a number of polypeptides that have anti-apoptotic activity or allow the virus to escape immune surveillance. 18,19 The E3 domain, a region that is nonessential for viral replication, is generally deleted to allow for the insertion of lengthy transgene expression cassettes without exceeding the genome size of wild-type virus, as this could potentially result in genetic instability of Ad vectors. 20 Ad vectors have been explored extensively as vaccine carriers for antigens of human immunodeficiency virus (HIV)-1, 21-25 the causative agent of the acquired immunodeficiency syndrome (AIDS). While initial efforts focused on expression of internal antigens for the induction of CD8 + T cell responses against HIV-1, efforts have since shifted toward expression of the envelope protein (Env). The heavily glycosylated and highly variable Env of HIV-1 forms trimers composed of glycoprotein (gp) 120 and gp41 on the surface of the virion. These complexes allow HIV-1 to attach to its receptors and coreceptors and are thereby essential for CD4 + cell infection by HIV-1. Env is not only the sole target of HIV-1-specif...

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Genetic Signatures of HIV-1 Envelope-mediated Bystander Apoptosis

Cited by 15 publications

References 87 publications

HIV-1 subtype CRF01_AE and B differ in utilization of low levels of CCR5, Maraviroc susceptibility and potential N-glycosylation sites

HIV-1 subtype CRF01_AE and B differ in utilization of low levels of CCR5, Maraviroc susceptibility and potential N-glycosylation sites

Duck tembusu virus and its envelope protein induce programmed cell death

A PartialE3Deletion in Replication-Defective Adenoviral Vectors Allows for Stable Expression of Potentially Toxic Transgene Products

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