Networking at the Level of Host Immunity: Immune Cell Interactions during Persistent Viral Infections

Ng, Cherie; Snell, Laura M.; Brooks, David G.; Oldstone, Michael B. A.

doi:10.1016/j.chom.2013.05.014

Cited by 77 publications

(76 citation statements)

References 150 publications

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“…T-helper cells are responsible for orchestrating an effective immune response that will ultimately result in viral clearance. By preventing appropriate interactions between APC and T-helper cells, these viruses are able to perpetuate viral replication and produce a state of anergy and immunotolerance (10). Thus, we theorize that since these two viruses share so many similar pathological mechanisms it is not unreasonable to speculate that they may share oncogenic properties that could act in a synergistic manner and promote the development of CRA.…”

Section: Discussionmentioning

confidence: 99%

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Association between chronic hepatitis C and hepatitis C/HIV co-infection and the development of colorectal adenomas

Hurtado-Cordovi

Davis-Yadley

Lipka

et al. 2016

J. Gastrointest. Oncol.

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Background: Limited knowledge exists about the effects chronic hepatitis C virus (HCV) infection has in the development of colorectal adenomas (CRA). Data regarding the association between chronic HIV infection and the development of CRA is scarce as well. We aim to determine if there is an association between the development of CRA and chronic infection with HCV and HCV/HIV co-infection.Methods: From July 1, 2009 to March 31, 2011 a total of 2,051 patients that underwent colonoscopy were included in our study. The population was divided into 2 study groups: those patients who tested positive for HCV, and HCV/HIC; the control groups consisted of patients whose results were negative. Fisher's exact χ 2 test for categorical variables and t-test for continuous variables was used to analyze data between groups.Logistic regression was performed to obtain odds ratios (OR).Results: CRA detection was higher in the HCV than in the control group (26.3% vs. 20.2%; P=1.02);Likewise, the incidence of CRA (25.5% vs. 20.8%; P=0.63) was higher in the co-infection group. However, in both of the study groups this difference was non-statistical.Conclusions: A higher detection rate of CRP was seen in the HCV population; however, it failed to reach statistical significance. Whether co-infection with HIV/HCV increases the incidence of CRA and/ or has a synergistic effect remains to be determined. The small sample population and the retrospective single institution nature of our study, as well as other confounders may have contributed to our negative results. However, our findings question whether HCV and HIV/HCV co-infected patients will benefit from screening colonoscopy at an earlier age. This issue merits further investigation with a large multi-center prospective study.

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Section: Discussionmentioning

confidence: 99%

“…Unfortunately, in these patients, such malignancies present at an earlier age and usually follow a more aggressive course (8,9). The exact reasons for this observation are unknown; however, many experts hypothesize that it may be partly due to the profound immune disarrangement produced by the HIV virus in their hosts (10).…”

Section: Introductionmentioning

confidence: 99%

Association between chronic hepatitis C and hepatitis C/HIV co-infection and the development of colorectal adenomas

Hurtado-Cordovi

Davis-Yadley

Lipka

et al. 2016

J. Gastrointest. Oncol.

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“…There are at least 27 members that are geographically, serologically, and phylogenetically divided into Old World and New World arenaviruses (1). The prototypic lymphocytic choriomeningitis virus (LCMV) infection of mice has long been used as a valuable model with which to study viral persistence and virus-induced immunity and immunopathology (2,3). The arenavirus is composed of a total of four genes on two genomic RNA segments in opposite orientations (1).…”

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confidence: 99%

A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose

Dhanwani

Zhou

Huang

et al. 2016

J Virol

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Pichinde virus (PICV) is a bisegmented enveloped RNA virus that targets macrophages and dendritic cells (DCs) early in infection and induces strong innate and adaptive immunity in mice. We have developed a reverse genetics system to produce live recombinant PICV (strain P18) with a trisegmented RNA genome (rP18tri), which encodes all four PICV gene products and as many as two foreign genes. We have engineered the vector to express the green fluorescent protein (GFP) reporter gene (abbreviated as G in virus designations) and either the hemagglutination (HA [H]) or the nucleoprotein (NP [P]) gene of the influenza A/PR8 virus. The trisegmented viruses rP18tri-G/H and rP18tri-G/P showed slightly reduced growth in vitro and expressed HA and NP, respectively. Mice immunized with rP18tri-G/H were completely protected against lethal influenza virus challenge even 120 days after immunization. These rP18tri-based vectors could efficiently induce both neutralizing antibodies and antigen-specific T cell responses via different immunization routes. Interestingly, the immune responses were significantly increased upon a booster dose and remained at high levels even after three booster doses. In summary, we have developed a novel PICV-based live vaccine vector that can express foreign antigens to induce strong humoral and cell-mediated immunity and is ideal for a primeand-boost vaccination strategy. IMPORTANCE We have developed a novel Pichinde virus (PICV)-based live viral vector, rP18tri, that packages three RNA segments and encodes as many as two foreign genes. Using the influenza virus HA and NP genes as model antigens, we show that this rP18tri vector can induce strong humoral and cellular immunity via different immunization routes and can lead to protection in mice. Interestingly, a booster dose further enhances the immune responses, a feature that distinguishes this from other known live viral vectors. In summary, our study demonstrates a unique feature of this live rP18tri vector to be used as a novel vaccine platform for a prime-and-boost vaccination strategy.A renaviruses are enveloped RNA viruses with a bisegmented genome and mostly use rodents as natural hosts. There are at least 27 members that are geographically, serologically, and phylogenetically divided into Old World and New World arenaviruses (1). The prototypic lymphocytic choriomeningitis virus (LCMV) infection of mice has long been used as a valuable model with which to study viral persistence and virus-induced immunity and immunopathology (2, 3). The arenavirus is composed of a total of four genes on two genomic RNA segments in opposite orientations (1). The Z protein, produced from the large (L) genomic segment, is a small RING domain-containing matrix protein that mediates virus budding, regulates viral RNA synthesis, and mediates host immune suppression (4, 5). The large L protein (ϳ200 kDa), also encoded on the L segment, is the RNA-dependent RNA polymerase (RdRp), which is required for viral RNA synthesis (6). The glycoprotein (GPC), encoded...

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“…An ensuing disruption in epithelial barrier function is associated with microbial translocation and chronic immune activation that contributes to generalized immune dysfunction, a loss of CD4 ϩ T cell regenerative capacity, and an exhaustion of cellular responses (66). The host-pathogen relationship is further exacerbated in favor of the virus by a high mutation rate that enables HIV and SIV to escape from adaptive cellular and humoral immune responses (15,(67)(68)(69)(70)(71)(72)(73).…”

Section: Discussionmentioning

confidence: 99%

Elite Control, Gut CD4 T Cell Sparing, and Enhanced Mucosal T Cell Responses in Macaca nemestrina Infected by a Simian Immunodeficiency Virus Lacking a gp41 Trafficking Motif

Breed

Elser

Torben

et al. 2015

J Virol

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Deletion of Gly-720 and Tyr-721 from a highly conserved GYxxØ trafficking signal in the SIVmac239 envelope glycoprotein cytoplasmic domain, producing a virus termed ⌬GY, leads to a striking perturbation in pathogenesis in rhesus macaques (Macaca mulatta). Infected macaques develop immune activation and progress to AIDS, but with only limited and transient infection of intestinal CD4؉ T cells and an absence of microbial translocation. Here we evaluated ⌬GY in pig-tailed macaques (Macaca nemestrina), a species in which SIVmac239 infection typically leads to increased immune activation and more rapid progression to AIDS than in rhesus macaques. In pig-tailed macaques, ⌬GY also replicated acutely to high peak plasma RNA levels identical to those for SIVmac239 and caused only transient infection of CD4 ؉ T cells in the gut lamina propria and no microbial translocation. However, in marked contrast to rhesus macaques, 19 of 21 pig-tailed macaques controlled ⌬GY replication with plasma viral loads of <15 to 50 RNA copies/ml. CD4 ؉ T cells were preserved in blood and gut for up to 100 weeks with no immune activation or disease progression. Robust antiviral CD4 ؉ T cell responses were seen, particularly in the gut. Anti-CD8 antibody depletion demonstrated CD8؉ cellular control of viral replication. Two pig-tailed macaques progressed to disease with persisting viremia and possible compensatory mutations in the cytoplasmic tail. These studies demonstrate a marked perturbation in pathogenesis caused by ⌬GY's ablation of the GYxxØ trafficking motif and reveal, paradoxically, that viral control is enhanced in a macaque species typically predisposed to more pathogenic manifestations of simian immunodeficiency virus (SIV) infection. IMPORTANCE The pathogenesis of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) reflects a balance between viral replication, host innate and adaptive antiviral immune responses, and sustained immune activation that in humans andAsian macaques is associated with persistent viremia, immune escape, and AIDS. Among nonhuman primates, pig-tailed macaques following SIV infection are predisposed to more rapid disease progression than are rhesus macaques. Here, we show that disruption of a conserved tyrosine-based cellular trafficking motif in the viral transmembrane envelope glycoprotein cytoplasmic tail leads in pig-tailed macaques to a unique phenotype in which high levels of acute viral replication are followed by elite control, robust cellular responses in mucosal tissues, and no disease. Paradoxically, control of this virus in rhesus macaques is only partial, and progression to AIDS occurs. This novel model should provide a powerful tool to help identify host-specific determinants for viral control with potential relevance for vaccine development.

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Networking at the Level of Host Immunity: Immune Cell Interactions during Persistent Viral Infections

Cited by 77 publications

References 150 publications

Association between chronic hepatitis C and hepatitis C/HIV co-infection and the development of colorectal adenomas

Association between chronic hepatitis C and hepatitis C/HIV co-infection and the development of colorectal adenomas

A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose

Elite Control, Gut CD4 T Cell Sparing, and Enhanced Mucosal T Cell Responses in Macaca nemestrina Infected by a Simian Immunodeficiency Virus Lacking a gp41 Trafficking Motif

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