Vaccinia Virus Envelope H3L Protein Binds to Cell Surface Heparan Sulfate and Is Important for Intracellular Mature Virion Morphogenesis and Virus Infection In Vitro and In Vivo

Lin, Chi-Long; Chung, Che-Sheng; Heine, H.G.; Chang, Wen

doi:10.1128/jvi.74.7.3353-3365.2000

Cited by 267 publications

(258 citation statements)

References 65 publications

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“…Whether these four proteins are sufficient for entry and fusion remains to be determined. In addition to the required entry/fusion proteins, the A27, D8, and H3 proteins may participate in the initial attachment step by binding to glycosaminoglycans (5,19,23). The presence of A28, H2, A21, and L5 orthologs in all poxviruses analyzed to date and the requirement for each during entry of vaccinia virus suggests that no functional redundancy exists among them.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, there is no evidence for fusion of the extracellular enveloped virion membrane, which is likely disrupted prior to or during virus entry. Three glycosaminoglycan-binding proteins (D8, H3, and A27) may facilitate initial binding of intracellular mature virions to the plasma membrane (5,19,23) but are not required for cell entry. Instead, three other intracellular mature virion membrane proteins (A28, H2, and A21) are not individually required for cell attachment but are needed for neutral pH entry and low-pH-induced cell-cell fusion mediated by intracellular mature virions as well as for cell-to-cell spread and fusion mediated by cell-associated extracellular enveloped virions (30,32,40).…”

mentioning

confidence: 99%

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The Product of the Vaccinia Virus L5R Gene Is a Fourth Membrane Protein Encoded by All Poxviruses That Is Required for Cell Entry and Cell-Cell Fusion

Townsley

Senkevich

Moss

2005

J Virol

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The L5R gene of vaccinia virus is conserved among all sequenced members of the Poxviridae but has no predicted function or recognized nonpoxvirus homolog. Here we provide the initial characterization of the L5 protein. L5 is expressed following DNA replication with kinetics typical of a viral late protein, contains a single intramolecular disulfide bond formed by the virus-encoded cytoplasmic redox pathway, and is incorporated into intracellular mature virus particles, where it is exposed on the membrane surface. To determine whether L5 is essential for virus replication, we constructed a mutant that synthesizes L5 only in the presence of an inducer. The mutant exhibited a conditional-lethal phenotype, as cell-to-cell virus spread and formation of infectious progeny were dependent on the inducer. Nevertheless, all stages of replication occurred in the absence of inducer and intracellular and extracellular progeny virions appeared morphologically normal. Noninfectious virions lacking L5 could bind to cells, but the cores did not enter the cytoplasm. In addition, virions lacking L5 were unable to mediate low-pH-triggered cell-cell fusion from within or without. The phenotype of the L5R conditional lethal mutant is identical to that of recently described mutants in which expression of the A21, A28, and H2 genes is repressed. Thus, L5 is the fourth component of the poxvirus cell entry/fusion apparatus that is required for entry of both the intracellular and extracellular infectious forms of vaccinia virus.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Product of the Vaccinia Virus L5R Gene Is a Fourth Membrane Protein Encoded by All Poxviruses That Is Required for Cell Entry and Cell-Cell Fusion

Townsley

Senkevich

Moss

2005

J Virol

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“…To explore this issue in greater detail, we were interested in tracking Ab responses to an individual VV protein, and we identified H3L as a good candidate protein. H3L is a VV integral membrane protein that has been identified as a target of human Ab responses and is likely to be involved in virus adsorption to cell surfaces (15). Serum samples from our study were therefore tested for Abs specific for H3L.…”

Section: Memory B Cell Recall Responses After Revaccinationmentioning

confidence: 99%

Cutting Edge: Long-Term B Cell Memory in Humans after Smallpox Vaccination

Crotty

Felgner

Davies

et al. 2003

The Journal of Immunology

612

508

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Memory B cells are a central component of humoral immunity, and yet little is known about their longevity in humans. Immune memory after smallpox vaccination (DryVax) is a valuable benchmark for understanding the longevity of B cell memory in the absence of re-exposure to Ag. In this study, we demonstrate that smallpox vaccine-specific memory B cells last for >50 years in immunized individuals. Virus-specific memory B cells initially declined postimmunization, but then reached a plateau ∼10-fold lower than peak and were stably maintained for >50 years after vaccination at a frequency of ∼0.1% of total circulating IgG+ B cells. These persisting memory B cells were functional and able to mount a robust anamnestic Ab response upon revaccination. Additionally, virus-specific CD4+ T cells were detected decades after vaccination. These data show that immunological memory to DryVax vaccine is long-lived and may contribute to protection against smallpox.

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“…These include major envelope genes of BPXV homologues of VACV genes viz. envelope proteins that bind cellular heparan sulfate (H3L and A27L) and chondroitin sulfate (D8L), which play prime role in VACV attachment and cell entry [21]. Nucleic acid sequences of selected genes of BPXV isolates showed [99 % sequence identity not only among themselves but also with VACV.…”

Section: Sequence and Phylogenetic Analyses Studies On Bpxvmentioning

confidence: 99%

Emergence and Reemergence of Vaccinia-Like Viruses: Global Scenario and Perspectives

et al. 2012

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Vaccinia Virus Envelope H3L Protein Binds to Cell Surface Heparan Sulfate and Is Important for Intracellular Mature Virion Morphogenesis and Virus Infection In Vitro and In Vivo

Cited by 267 publications

References 65 publications

The Product of the Vaccinia Virus L5R Gene Is a Fourth Membrane Protein Encoded by All Poxviruses That Is Required for Cell Entry and Cell-Cell Fusion

The Product of the Vaccinia Virus L5R Gene Is a Fourth Membrane Protein Encoded by All Poxviruses That Is Required for Cell Entry and Cell-Cell Fusion

Cutting Edge: Long-Term B Cell Memory in Humans after Smallpox Vaccination

Emergence and Reemergence of Vaccinia-Like Viruses: Global Scenario and Perspectives

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