The hr1 and Fusion Peptide Regions of the Subgroup B Avian Sarcoma and Leukosis Virus Envelope Glycoprotein Influence Low pH-Dependent Membrane Fusion

Babel, Angeline Rose; Bruce, James W.; Young, John A. T.

doi:10.1371/journal.pone.0000171

Cited by 9 publications

(6 citation statements)

References 39 publications

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“…Alterations in the fusion peptide have also been observed in other ASLV mutants. A study (44) selected for ASLV with a decreased pH threshold of membrane fusion activation, revealing that mutations in hr1 and in the fusion peptide region influence the threshold. Its authors suggest that the increased acid requirement exhibited by mutants may be due to their increased stability.…”

Section: Discussionmentioning

confidence: 99%

Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry

Lounková

Kosla

Přikryl

et al. 2017

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

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The extent of virus transmission among individuals and species is generally determined by the presence of specific membraneembedded virus receptors required for virus entry. Interaction of the viral envelope glycoprotein (Env) with a specific cellular receptor is the first and crucial step in determining host specificity. Using a well-established retroviral model-avian Rous sarcoma virus (RSV)-we analyzed changes in an RSV variant that had repeatedly been able to infect rodents. By envelope gene (env) sequencing, we identified eight mutations that do not match the already described mutations influencing the host range. Two of these mutations-one at the beginning (D32G) of the surface Env subunit (SU) and the other at the end of the fusion peptide region (L378S)-were found to be of critical importance, ensuring transmission to rodent, human, and chicken cells lacking the appropriate receptor. Furthermore, we carried out assays to examine the virus entry mechanism and concluded that these two mutations cause conformational changes in the Env variant and that these changes lead to an activated, or primed, state of Env (normally induced after Env interaction with the receptor). In summary, our results indicate that retroviral host range extension is caused by spontaneous Env activation, which circumvents the need for original cell receptor. This activation is, in turn, caused by mutations in various env regions.Rous sarcoma virus | retrovirus | virus entry | envelope glycoprotein | receptor-independent entry T he emergence of novel infectious diseases is often associated with cross-species virus transmission. For example, wildlife viruses have caused such severe human diseases as AIDS, Ebola, severe acute respiratory syndrome (SARS), and influenza. However, the genetic mechanisms determining how viruses cross the species boundary and adapt to new hosts have not been properly understood (1). The ability of a virus to enter the host cell is the first and crucial step in determining host specificity. Viruses causing the above-mentioned diseases possess envelope class I fusion glycoproteins, and their entry into the host cell shares very similar features. There may be a yet unidentified universal mechanism of cross-species transmission.For decades, avian retrovirus Rous sarcoma virus (RSV) has been a driving force in efforts to understand acutely transforming retroviruses. The establishment of proper cell culture conditions and an in vitro assay of RSV transforming activity have led to a generally accepted description of retrovirus entry, replication, composition, and genetics (2).RSV belongs to avian sarcoma and leukosis viruses (ASLVs), which are part of the alpharetrovirus genus. RSV and the other ASLVs naturally infect only avian species; however, experimental RSV infection was achieved in hamsters and rats. Studies of RSV transforming activity in mammalian cells enabled the discovery of the tight association that exists between the viral genome and the genome of the transformed cell and corresponds to the RSV provi...

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Section: Discussionmentioning

confidence: 99%

Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry

Lounková

Kosla

Přikryl

et al. 2017

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

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“…Some mutations within the fusion peptide of gp37 have been associated with fusion activation of env protein (Babel et al, 2007). The lack of the 19-bp insertion in the U3 region of FJ15HT0 suggested this isolate is possibly associated with ALV-J strains inducing ML (Wei et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

A novel avian retrovirus associated with lymphocytoma isolated from a local Chinese flock induced significantly reduced growth and immune suppression in SPF chickens

Zhao

Zeng

et al. 2017

Veterinary Microbiology

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“…Hence it has been postulated that low pH does for ASLV Env what the internal thiol disulfide exchange motif does for MoMLV Env , that is to move the SU head domains sufficiently away from the fusion subunit to allow the membrane-embedded prehairpin to fold-back to its final trimer-of-hairpins conformation. Key remaining issues include the identification of residues critical for the pH-induced conversion of the prehairpin to the trimer-of-hairpins conformation (Babel et al, 2007), and determining whether ASLV Env employs a chain reversal reaction similar to that proposed for other retroviral Env glycoproteins (Maerz et al, 2000(Maerz et al, , 2001.…”

Section: Receptor Binding Followed By Low Ph: the Case Of Avian Retromentioning

confidence: 99%

Structures and Mechanisms of Viral Membrane Fusion Proteins: Multiple Variations on a Common Theme

White

Delos

Brecher

et al. 2008

Critical Reviews in Biochemistry and Molecular Biology

775

942

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Recent work has identified three distinct classes of viral membrane fusion proteins based on structural criteria. In addition, there are at least four distinct mechanisms by which viral fusion proteins can be triggered to undergo fusion-inducing conformational changes. Viral fusion proteins also contain different types of fusion peptides and vary in their reliance on accessory proteins. These differing features combine to yield a rich diversity of fusion proteins. Yet despite this staggering diversity, all characterized viral fusion proteins convert from a fusion-competent state (dimers or trimers, depending on the class) to a membrane-embedded homotrimeric prehairpin, and then to a trimer-ofhairpins that brings the fusion peptide, attached to the target membrane, and the transmembrane domain, attached to the viral membrane, into close proximity thereby facilitating the union of viral and target membranes. During these conformational conversions, the fusion proteins induce membranes to progress through stages of close apposition, hemifusion, and then the formation of small, and finally large, fusion pores. Clearly, highly divergent proteins have converged on the same overall strategy to mediate fusion, an essential step in the life cycle of every enveloped virus.

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The hr1 and Fusion Peptide Regions of the Subgroup B Avian Sarcoma and Leukosis Virus Envelope Glycoprotein Influence Low pH-Dependent Membrane Fusion

Cited by 9 publications

References 39 publications

Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry

Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry

A novel avian retrovirus associated with lymphocytoma isolated from a local Chinese flock induced significantly reduced growth and immune suppression in SPF chickens

Structures and Mechanisms of Viral Membrane Fusion Proteins: Multiple Variations on a Common Theme

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