HIV-1 Tat modulates T-bet expression and induces Th1 type of immune response

Kulkarni, Asavari; Ravi, Dyavar S.; Singh, Kamini; Rampalli, Shravanti; Parekh, Vrajesh V.; Mitra, Debashis; Chattopadhyay, Samit

doi:10.1016/j.bbrc.2005.02.042

Cited by 6 publications

(5 citation statements)

References 25 publications

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“…These results are in agreement with the observation that the Tbx21 mRNA level is suppressed in HCVinfected T cells (19). Tbx21 is required for protection against human viral infection (6,21,31,44). The principal function of Tbx21 in developing Th1 cells is to negatively regulate Gata-3 (50).…”

Section: Discussionsupporting

confidence: 90%

Inhibition of Intrahepatic Gamma Interferon Production by Hepatitis C Virus Nonstructural Protein 5A in Transgenic Mice

Kanda

Steele²,

Ray

2009

J Virol

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Hepatitis C virus (HCV) utilizes strategies to suppress or evade the host immune response for establishment of persistent infection. We have shown previously that HCV nonstructural protein 5A (NS5A) impairs tumor necrosis factor alpha (TNF-␣)-mediated apoptosis. In this study, we have examined the immunomodulatory role of HCV NS5A protein in transgenic mouse (NS5A-Tg) liver when mice were challenged with an unrelated hepatotropic adenovirus as a nonspecific stimulus. Hepatotropic adenovirus was introduced intravenously into NS5A-Tg mice and control mice, and virus clearance from liver was compared over a time course of 3 weeks. The differential mRNA expression levels of 84 cytokine-related genes, signal pathway molecules, transcription factors, and cell surface molecules were determined using real-time reverse transcription-PCR array. NS5A-Tg mice failed to clear adenovirus from liver up to 3 weeks postinfection while control mice cleared virus within 1 to 2 weeks. Subsequent study revealed that gamma interferon (IFN-␥) expression is inhibited at both the mRNA and protein levels in NS5A-Tg mice, and an inverse expression of transcription factors Gata-3 and Tbx21 is observed. However, TNF-␣ mRNA and protein expression were elevated in both NS5A-Tg and control mice. Together, our results suggested that HCV NS5A acts as an immunomodulator by inhibiting IFN-␥ production and may play an important role toward establishment of chronic HCV infection.

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Section: Discussionsupporting

confidence: 90%

Inhibition of Intrahepatic Gamma Interferon Production by Hepatitis C Virus Nonstructural Protein 5A in Transgenic Mice

Kanda

Steele²,

Ray

2009

J Virol

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“…In addition, Tat has been shown to up-regulate the expression of the transcription factor T-bet [82], which is crucial for HSV control [83], [84], and this may enable Tat to promote Th1 responses and class-switch recombination to the IgG 2a isotype in B cells [85], [86]. Consistent with these observations, our data clearly demonstrate that Tat induces enhancement of IFN-γ release – while dampening Th-2 responses against HSV antigens (Figure 6, 7) – and promotes the production of IgG 2a associated with Th1-type responses (Figure 8).…”

Section: Discussionmentioning

confidence: 99%

An Attenuated Herpes Simplex Virus Type 1 (HSV1) Encoding the HIV-1 Tat Protein Protects Mice from a Deadly Mucosal HSV1 Challenge

et al. 2014

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Herpes simplex virus types 1 and 2 (HSV1 and HSV2) are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat). In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ), induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1 infection and dissemination.

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“…During the establishment of HIV-1 infection, the Th1 response is induced early during the establishment of the virus in the host. The binding of the HIV-1 transcription activator Tat to CD4+ T cells induces vigorous proliferation of CD4+ T cells as well as IFN-γ production and T-bet expression, which lead to the activation of other cells that can limit viral replication (Kulkarni et al, 2005). A protective role for T-bet has also been suggested in Dengue fever, whereby patients with hemorrhagic dengue fever have significantly lower levels of T-bet and IFN-γ than patients who lack hemorrhagic symptoms, suggesting an important role for T-bet in the regulation of disease severity (Chen et al, 2005).…”

Section: Viral Infectionsmentioning

confidence: 99%

Role of IFN-α/β signaling in the prevention of genital herpes virus type 2 infection

Svensson

Bellner

Magnusson

et al. 2007

Journal of Reproductive Immunology

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Genital herpes, caused by herpes simplex virus type 2 (HSV-2), is the most common genital ulcer disease worldwide. HSV-2 infection causes a variety of symptoms, ranging from subclinical/silent infection to severe and recurrent episodes of genital blisters and ulcers, and the virus can also in rare cases cause meningitis. In primary infection, the virus sequentially enters and replicates in epithelial cells followed by local sensory neurons. In the latter, a life-long infection is established via the induction of viral latency or dormancy. Latent virus is however continuously reactivated, also in those with a silent infection, which results in a low-grade viral replication and shedding into the vaginal lumen. This reactivation can in many individuals be amplified following e.g. stress, hormonal variations or immune suppression, which results in recurrent genital disease.

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HIV-1 Tat modulates T-bet expression and induces Th1 type of immune response

Cited by 6 publications

References 25 publications

Inhibition of Intrahepatic Gamma Interferon Production by Hepatitis C Virus Nonstructural Protein 5A in Transgenic Mice

Inhibition of Intrahepatic Gamma Interferon Production by Hepatitis C Virus Nonstructural Protein 5A in Transgenic Mice

An Attenuated Herpes Simplex Virus Type 1 (HSV1) Encoding the HIV-1 Tat Protein Protects Mice from a Deadly Mucosal HSV1 Challenge

Role of IFN-α/β signaling in the prevention of genital herpes virus type 2 infection

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