Recombinant influenza virus expressing HIV-1 p24 capsid protein induces mucosal HIV-specific CD8 T-cell responses

Tan, Hyon-Xhi; Gilbertson, Brad; Jegaskanda, Sinthujan; Alcântara, Sheilajen; Amarasena, Thakshila; Stambas, John; McAuley, Julie; Kent, Stephen J.; Rose, Robert De

doi:10.1016/j.vaccine.2016.01.030

Cited by 14 publications

(16 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PR8 gfp is a reverse engineered PR8 virus that encodes green fluorescent protein (GFP) within the NS gene segment. 50 Viruses were amplified in eggs and the allantoic fluid was assayed for infectious virus by plaque formation in Madin Darby canine kidney (MDCK) cells 51 and expressed as PFU per ml.…”

Section: Methodsmentioning

confidence: 99%

The cell surface mucin MUC1 limits the severity of influenza A virus infection

et al. 2017

View full text Add to dashboard Cite

Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency. Utilizing human lung epithelial cells, we found that IAV associates with the cs-mucin MUC1 but not MUC13 or MUC16. Overexpression of MUC1 by epithelial cells or the addition of sialylated synthetic MUC1 constructs, reduced IAV infection in vitro. In addition, Muc1 À / À mice infected with IAV exhibited enhanced morbidity and mortality, as well as greater inflammatory mediator responses compared to wild type mice. This study implicates the cs-mucin MUC1 as a critical and dynamic component of the innate host response that limits the severity of influenza and provides the foundation for exploration of MUC1 in resolving inflammatory disease.

show abstract

Section: Methodsmentioning

confidence: 99%

The cell surface mucin MUC1 limits the severity of influenza A virus infection

et al. 2017

View full text Add to dashboard Cite

show abstract

“…H1N1 (Flu(PR8)-p24) or H3N2 (Flu(X31)-p24) subtype recombinant influenza viruses expressing the HIV-1 subtype B Gag p24 capsid gene were developed as described previously. 32 Mice were anesthetized by isoflurane inhalation before immunizations. Intranasal immunization was performed with 10 5 p.f.u./50 ml of Flu(PR8)-p24 virus.…”

Section: Methodsmentioning

confidence: 99%

“…We recently developed recombinant influenza viruses expressing the HIV-1 Gag protein p24. 32 To induce CD8 T-cell immunity in the vaginal mucosa, a immunization regimen consisting of an intranasal prime followed by an intravaginal boost was performed. Intranasal immunization can prime cytotoxic T lymphocyte responses in the vaginal mucosa, which can be subsequently boosted by vaginal immunization.…”

Section: Intravaginal Boosting Induces Vaginal Mucosal Hiv-specific Cmentioning

confidence: 99%

“…Overall, HIV-specific CD8 T-cell responses were significantly elevated in Flu-p24-immunized mice for all tissues investigated vs. mock-immunized mice (Figure 1d), and are consistent with previous observations. 32 CD103, a marker of tissue residency, was examined in all tissue compartments (Figure 1c,e). CD103 expression was significantly increased in HIV-specific CD8 T cells of the vaginal mucosa compared with lung BAL samples, and was negligible in blood.…”

Section: Intravaginal Boosting Induces Vaginal Mucosal Hiv-specific Cmentioning

confidence: 99%

See 1 more Smart Citation

Induction of vaginal-resident HIV-specific CD8 T cells with mucosal prime–boost immunization

et al. 2018

View full text Add to dashboard Cite

Tissue-resident memory (T) CD8 T cells survey a range of non-lymphoid mucosal tissues where they rapidly mediate clearance of viral infections at the entry portals. Vaccines that establish CD8 T cells in the cervicovaginal mucosa hold promise for effective immunity against sexually transmitted HIV. We demonstrate that HIV-specific CD8 T cells can be established in the murine vaginal mucosa using a combined intranasal and intravaginal mucosal immunization with recombinant influenza-HIV vectors. Using in situ tetramer immunofluorescence microscopy, we found that this mucosally administered prime-boost immunization also resulted in the durable seeding of CD8 T cells in the frontline vaginal epithelial compartment as opposed to the vaginal submucosa. Upon cognate antigen recognition within the vaginal mucosa, these HIV-specific CD8 T cells rapidly initiated a tissue-wide state of immunity. The activation of HIV-specific CD8 T cells resulted in the upregulation of endothelial vessel addressin expression and substantial recruitment of both adaptive and innate immune cells in the vaginal mucosa. These findings suggest that the epithelial localization of HIV-specific CD8 T cell populations and their capacity to rapidly activate both arms of the immune system could significantly augment frontline defenses against vaginal HIV infection.

show abstract

“…Aphthovirus -like 2A has been used to express transgenes in multiple circumstances. It can be used in oncolytic adenoviruses (Funston et al, 2008), lentiviral vectors (Chinnasamy et al, 2006), retroviral vectors (de Felipe et al, 1999), recombinant adeno-associated viruses (Furler et al, 2001), and influenza virus vectors (Tan et al, 2016) to express multicistronic genes.…”

Section: Mechanism and Function Mediated By Aphthovirus-like 2a Peptidementioning

confidence: 99%

Structures and Corresponding Functions of Five Types of Picornaviral 2A Proteins

et al. 2017

View full text Add to dashboard Cite

Among the few non-structural proteins encoded by the picornaviral genome, the 2A protein is particularly special, irrespective of structure or function. During the evolution of the Picornaviridae family, the 2A protein has been highly non-conserved. We believe that the 2A protein in this family can be classified into at least five distinct types according to previous studies. These five types are (A) chymotrypsin-like 2A, (B) Parechovirus-like 2A, (C) hepatitis-A-virus-like 2A, (D) Aphthovirus-like 2A, and (E) 2A sequence of the genus Cardiovirus. We carried out a phylogenetic analysis and found that there was almost no homology between each type. Subsequently, we aligned the sequences within each type and found that the functional motifs in each type are highly conserved. These different motifs perform different functions. Therefore, in this review, we introduce the structures and functions of these five types of 2As separately. Based on the structures and functions, we provide suggestions to combat picornaviruses. The complexity and diversity of the 2A protein has caused great difficulties in functional and antiviral research. In this review, researchers can find useful information on the 2A protein and thus conduct improved antiviral research.

show abstract

Recombinant influenza virus expressing HIV-1 p24 capsid protein induces mucosal HIV-specific CD8 T-cell responses

Cited by 14 publications

References 46 publications

The cell surface mucin MUC1 limits the severity of influenza A virus infection

The cell surface mucin MUC1 limits the severity of influenza A virus infection

Induction of vaginal-resident HIV-specific CD8 T cells with mucosal prime–boost immunization

Structures and Corresponding Functions of Five Types of Picornaviral 2A Proteins

Contact Info

Product

Resources

About