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12 pages, 1547 KiB

Open AccessArticle

Characterization of EIAV env Quasispecies during Long-Term Passage In Vitro: Gradual Loss of Pathogenicity

by Cong Liu, Xue-Feng Wang, Yan Wang, Jie Chen, Zhaohua Zhong, Yuezhi Lin and Xiaojun Wang

Viruses 2019, 11(4), 380; https://doi.org/10.3390/v11040380 - 24 Apr 2019

Cited by 4 | Viewed by 3048

Abstract

As the only widely used live lentiviral vaccine, the equine infectious anima virus (EIAV) attenuated vaccine was developed by in vitro passaging of a virulent strain for 121 generations. In our previous study, we observed that the attenuated vaccine was gradually selected under [...] Read more.

As the only widely used live lentiviral vaccine, the equine infectious anima virus (EIAV) attenuated vaccine was developed by in vitro passaging of a virulent strain for 121 generations. In our previous study, we observed that the attenuated vaccine was gradually selected under increased environmental pressure at the population level (termed a quasispecies). To further elucidate the potential correlation between viral quasispecies evolution and pathogenesis, a systematic study was performed by sequencing env using several methods. Some key mutations were identified within Env, and we observed that increased percentages of these mutations were accompanied by an increased passage number and attenuated virulence. Phylogenetic analysis revealed that env mutations related to the loss of virulence might have occurred evolutionarily. Among these mutations, deletion of amino acid 236 in the V4 region of Env resulted in the loss of one N-glycosylation site that was crucial for virulence. Notably, the 236-deleted sequence represented a “vaccine-specific” mutation that was also found in wild EIAV_LN40 strains based on single genome amplification (SGA) analysis. Therefore, our results suggest that the EIAV attenuated vaccine may originate from a branch of quasispecies of EIAV_LN40. Generally, the presented results may increase our understanding of the attenuation mechanism of the EIAV vaccine and provide more information about the evolution of other lentiviruses. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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15 pages, 248 KiB

Open AccessArticle

Comparative Analysis of Different Serological and Molecular Tests for the Detection of Small Ruminant Lentiviruses (SRLVs) in Belgian Sheep and Goats

by Rodolphe Michiels, Eva Van Mael, Christian Quinet, Nadjah Radia Adjadj, Ann Brigitte Cay and Nick De Regge

Viruses 2018, 10(12), 696; https://doi.org/10.3390/v10120696 - 08 Dec 2018

Cited by 32 | Viewed by 3401

Abstract

Countries rely on good diagnostic tests and appropriate testing schemes to fight against economically important small ruminant lentivirus (SRLV) infections. We undertook an extensive comparative analysis of seven commercially available serological tests and one in-house real-time PCR (qPCR) detecting genotype A and B [...] Read more.

Countries rely on good diagnostic tests and appropriate testing schemes to fight against economically important small ruminant lentivirus (SRLV) infections. We undertook an extensive comparative analysis of seven commercially available serological tests and one in-house real-time PCR (qPCR) detecting genotype A and B strains using a large panel of representative Belgian field samples and samples from experimentally infected sheep and goats. ELISAs generally performed well and detected seroconversion within three weeks post experimental infection. Two enzyme-linked immunosorbent assays (ELISAs) (Elitest and IDscreen^® kits) showed the highest sensitivities (>96%) and specificities (>95%) in both species, and their combined use allowed to correctly identify the infection status of all animals. Individual agar gel immunodiffusion (AGIDs) kits lacked sensitivity, but interestingly, the combined use of both kits had a sensitivity and specificity of 100%. qPCRs detected SRLV infection before seroconversion at two weeks post infection and showed a specificity of 100%. Sensitivity however remained suboptimal at 85%. These results allow to propose a faster and cheaper diagnostic testing strategy for Belgium by combining a first ELISA screening, followed by confirmation of positive samples in AGID and/or a second ELISA. Since genotypes A and B strains are predominant in many countries, these results are interesting for other countries implementing SRLV control programs. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

7 pages, 732 KiB

Open AccessCommunication

Transcriptome Analysis and In Situ Hybridization for FcaGHV1 in Feline Lymphoma

by Mahdis Aghazadeh, Mang Shi, Patricia A. Pesavento, Amy C. Durham, Tamsen Polley, Shannon L. Donahoe, Ryan M. Troyer, Vanessa R. Barrs, Edward C. Holmes and Julia A. Beatty

Viruses 2018, 10(9), 464; https://doi.org/10.3390/v10090464 - 30 Aug 2018

Cited by 6 | Viewed by 3936

Abstract

Lymphoma is one of the most common malignancies in domestic cats. The lymphomagenic potential of Felis catus gammaherpesvirus 1 (FcaGHV1), a common infection in domestic cats, is unknown. In other species, including humans, cellular transformation by gammaherpesviruses is typically mediated by viral genes [...] Read more.

Lymphoma is one of the most common malignancies in domestic cats. The lymphomagenic potential of Felis catus gammaherpesvirus 1 (FcaGHV1), a common infection in domestic cats, is unknown. In other species, including humans, cellular transformation by gammaherpesviruses is typically mediated by viral genes expressed during latency. We analysed tumour RNA, from diffuse large B-cell lymphomas (DLBCL) appearing in cats coinfected with FcaGHV1 and feline immunodeficiency virus (FIV) (n = 10), by high throughput transcriptome sequencing and reverse transcription PCR. A limited repertoire of FcaGHV transcripts was identified in five tumors, including homologs of oncogenic latency-associated transcripts, latency-associated nuclear antigen (LANA, ORF73) and vFLIP (F7), lytic genes (ORF50, ORF6, ORF59, F10), and an ORF unique to FcaGHV1, F20. In situ hybridization of FIV-associated DLBCLs (n = 9), post-transplant lymphomas (n = 6) and high-grade B and T-cell intestinal lymphomas (n = 8) identified a single case in which FcaGHV1 nucleic acid was detectable. These results demonstrate that FcaGHV1 transcripts can be detected in some FIV-associated lymphomas, but at low copy number, precluding assessment of a potential role for FcaGHV1 in lymphomagenesis. Future investigation of the FcaGHV1 transcriptome in clinical samples might employ viral enrichment and greater sequencing depth to enhance the retrieval of viral reads. Our results suggest prioritization of a subset of intestinal T-cell tumors, large granular lymphocyte lymphoma, for study. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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10 pages, 223 KiB

Open AccessArticle

Enrichment Preferences of FIV-Infected and Uninfected Laboratory-Housed Cats

by Claudia J. Kennedy, Andrea E. Thomson, Emily H. Griffith, Jonathan Fogle, B. Duncan X. Lascelles, Rick B. Meeker, Barbara L. Sherman and Margaret E. Gruen

Viruses 2018, 10(7), 353; https://doi.org/10.3390/v10070353 - 03 Jul 2018

Cited by 7 | Viewed by 4562

Abstract

Environmental enrichment is critical for alleviating stress in laboratory felines. However, there is a paucity of information about suitable enrichment for cats. This study aimed to determine preferred enrichment options of individually-housed, castrated male domestic short hair cats (Felis catus) used [...] Read more.

Environmental enrichment is critical for alleviating stress in laboratory felines. However, there is a paucity of information about suitable enrichment for cats. This study aimed to determine preferred enrichment options of individually-housed, castrated male domestic short hair cats (Felis catus) used in a longitudinal study of the effects of chronic feline immunodeficiency virus (FIV) infection, and to determine if the FIV status of the cats affected enrichment preferences. Preference testing was performed with two types of grooming brushes, three different interactive play options, including a laser, ball, and petting interaction with a familiar investigator, and two types of toenail conditioning objects. We found that cats elected to be brushed, preferred social interaction and play with the laser to the ball, and preferred to scratch on an inclined-box toenail conditioning object compared to a horizontal, circular toenail conditioning object. There were individual preferences for enrichment opportunities. There were no differences in preferences between FIV-infected and sham-infected cats. These enrichment preferences may be used to advise laboratory animal facilities and researchers about how to best accommodate the behavioral needs of laboratory cats. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

15 pages, 2473 KiB

Open AccessArticle

Genetic Characterization and Phylogenetic Analysis of Small Ruminant Lentiviruses Detected in Spanish Assaf Sheep with Different Mammary Lesions

by Elena Gayo, Vincenzo Cuteri, Laura Polledo, Giacomo Rossi, Juan F. García Marín and Silvia Preziuso

Viruses 2018, 10(6), 315; https://doi.org/10.3390/v10060315 - 09 Jun 2018

Cited by 8 | Viewed by 3261

Abstract

Small Ruminant Lentiviruses (SRLVs) are widespread in many countries and cause economically relevant, slow, and persistent diseases in sheep and goats. Monitoring the genetic diversity of SRLVs is useful to improve the diagnostic tools used in the eradication programs. In this study, SRLVs [...] Read more.

Small Ruminant Lentiviruses (SRLVs) are widespread in many countries and cause economically relevant, slow, and persistent diseases in sheep and goats. Monitoring the genetic diversity of SRLVs is useful to improve the diagnostic tools used in the eradication programs. In this study, SRLVs detected in Spanish Assaf sheep with different grades of lymphoproliferative mastitis were sequenced. Genetic characterization showed that most samples belonged to type A and were closer to Spanish SRLV isolates previously classified as A2/A3. Four samples belonged to subtype B2 and showed higher homology with Italian B2 strains than with Spanish B2 isolates. Amino acid sequences of immuno-dominant epitopes in the gag region were very conserved while more alterations were found in the LTR sequences. No significant correlations were found between grades of mastitis and alterations in the sequences although samples with similar histological features were phylogenetically closer to each other. Broader genetic characterization surveys in samples with different grades of SRLV-lesions are required for evaluating potential correlations between SRLV sequences and the severity of diseases. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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12 pages, 1644 KiB

Open AccessArticle

Histone Modulation Blocks Treg-Induced Foxp3 Binding to the IL-2 Promoter of Virus-Specific CD8⁺ T Cells from Feline Immunodeficiency Virus-Infected Cats

by Mukta Nag, Yan Wang, Kristina De Paris and Jonathan E. Fogle

Viruses 2018, 10(6), 287; https://doi.org/10.3390/v10060287 - 27 May 2018

Viewed by 4004

Abstract

CD8⁺ T cells are critical for controlling HIV infection. During the chronic phase of lentiviral infection, CD8⁺ T cells lose their proliferative capacity and exhibit impaired antiviral function. This loss of CD8⁺ T cell function is due, in part, to [...] Read more.

CD8⁺ T cells are critical for controlling HIV infection. During the chronic phase of lentiviral infection, CD8⁺ T cells lose their proliferative capacity and exhibit impaired antiviral function. This loss of CD8⁺ T cell function is due, in part, to CD4⁺CD25⁺ T regulatory (Treg) cell-mediated suppression. Our research group has demonstrated that lentivirus-activated CD4⁺CD25⁺ Treg cells induce the repressive transcription factor forkhead box P3 (Foxp3) in autologous CD8⁺ T cells following co-culture. We have recently reported that Treg-induced Foxp3 binds the interleukin-2 (IL-2), interferon-γ (IFN- γ), and tumor necrosis factor-α (TNF-α) promoters in virus-specific CD8⁺ T cells. These data suggest an important role of Foxp3-mediated CD8⁺ T cell dysfunction in lentiviral infection. To elucidate the mechanism of this suppression, we previously reported that decreased methylation facilitates Foxp3 binding in mitogen-activated CD8⁺ T cells from feline immunodeficiency virus (FIV)-infected cats. We demonstrated the reduced binding of Foxp3 to the IL-2 promoter by increasing methylation of CD8⁺ T cells. In the studies presented here, we ask if another form of epigenetic modulation might alleviate Foxp3-mediated suppression in CD8⁺ T cells. We hypothesized that decreasing histone acetylation in virus-specific CD8⁺ T cells would decrease Treg-induced Foxp3 binding to the IL-2 promoter. Indeed, using anacardic acid (AA), a known histone acetyl transferase (HAT) inhibitor, we demonstrate a reduction in Foxp3 binding to the IL-2 promoter in virus-specific CD8⁺ T cells co-cultured with autologous Treg cells. These data identify a novel mechanism of Foxp3-mediated CD8⁺ T cell dysfunction during lentiviral infection. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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16 pages, 3829 KiB

Open AccessArticle

Multiple, Independent T Cell Lymphomas Arising in an Experimentally FIV-Infected Cat during the Terminal Stage of Infection

by Brian G. Murphy, Christina Eckstrand, Diego Castillo, Andre Poon, Molly Liepnieks, Kristy Harmon and Peter Moore

Viruses 2018, 10(6), 280; https://doi.org/10.3390/v10060280 - 24 May 2018

Cited by 9 | Viewed by 3341

Abstract

Our laboratory has serially reported on the virologic and immunopathologic features of a cohort of experimental feline immunodeficiency virus (FIV)-infected cats for more than eight years. At 8.09 years post infection (PI), one of these animals entered the terminal stage of infection, characterized [...] Read more.

Our laboratory has serially reported on the virologic and immunopathologic features of a cohort of experimental feline immunodeficiency virus (FIV)-infected cats for more than eight years. At 8.09 years post infection (PI), one of these animals entered the terminal stage of infection, characterized by undulating hyperthermia, progressive anorexia, weight loss, and pancytopenia; the animal was not responsive to therapeutic interventions, necessitating euthanasia six weeks later (8.20 years PI). Subsequent analyses indicated that neoplastic lymphocytes infiltrated multiple cervical lymph nodes and a band-like region of the mucosal lamina propria within a segment of the intestine. Immunohistochemistry and T cell clonality testing determined that the nodal and intestinal lesions were independently arising from CD3 T cell lymphomas. In-situ RNA hybridization studies indicated that diffuse neoplastic lymphocytes from the cervical lymph node contained abundant viral nucleic acid, while viral nucleic acid was not detectable in lymphocytes from the intestinal lymphoma lesion. The proviral long terminal repeat (LTR) was amplified and sequenced from multiple anatomic sites, and a common clone containing a single nucleotide polymorphism was determined to be defective in response to phorbol myristate acetate (PMA)-mediated promoter activation in a reporter gene assay. This assay revealed a previously unidentified PMA response element within the FIV U3 region 3’ to the TATA box. The possible implications of these results on FIV-lymphoma pathogenesis are discussed. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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11 pages, 1143 KiB

Open AccessArticle

An Immunodominant Region of the Envelope Glycoprotein of Small Ruminant Lentiviruses May Function as Decoy Antigen

by Marie-Luise Zahno and Giuseppe Bertoni

Viruses 2018, 10(5), 231; https://doi.org/10.3390/v10050231 - 02 May 2018

Cited by 5 | Viewed by 4688

Abstract

(1) Background: Small ruminant lentiviruses (SRLV) persist in infected goats that mount a strong humoral immune response characterized by low neutralizing titers. In this study, we characterized the antibody response to SU5, a variable, immunodominant epitope of the envelope glycoprotein of SRLV. We [...] Read more.

(1) Background: Small ruminant lentiviruses (SRLV) persist in infected goats that mount a strong humoral immune response characterized by low neutralizing titers. In this study, we characterized the antibody response to SU5, a variable, immunodominant epitope of the envelope glycoprotein of SRLV. We tested the working hypothesis that the variability of SU5 reflects escape from neutralizing antibody. (2) Methods: Affinity purified anti-SU5 antibody were tested for their neutralizing activity to the homologous lentivirus. Virus culture supernatant—in native form or following sonication and filtration—was used to test the ability of free envelope glycoproteins to compete for binding in a SU5-peptide-ELISA. (3) Results: Anti-SU5 antibodies are not neutralizing, strongly suggesting that they do not bind intact viral particles. In contrast, shed envelope glycoproteins efficiently compete for binding in a SU5-ELISA, providing convincing evidence that the SU5 epitope is exposed only on shed envelope glycoproteins. (4) Conclusions: Our results show that the antibody engaging SU5 is not neutralizing and does not appear to bind to SU expressed at the surface of virus particles. We propose that SU5 is a potential decoy epitope exposed on shaded envelope glycoproteins, luring the humoral immune response in committing an original antigenic sin to a functionally irrelevant epitope. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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Graphical abstract

15 pages, 1926 KiB

Open AccessArticle

Prior Puma Lentivirus Infection Modifies Early Immune Responses and Attenuates Feline Immunodeficiency Virus Infection in Cats

by Wendy S. Sprague, Ryan M. Troyer, Xin Zheng, Britta A. Wood, Martha Macmillan, Scott Carver and Susan VandeWoude

Viruses 2018, 10(4), 210; https://doi.org/10.3390/v10040210 - 20 Apr 2018

Cited by 4 | Viewed by 4706

Abstract

We previously showed that cats that were infected with non-pathogenic Puma lentivirus (PLV) and then infected with pathogenic feline immunodeficiency virus (FIV) (co-infection with the host adapted/pathogenic virus) had delayed FIV proviral and RNA viral loads in blood, with viral set-points that were [...] Read more.

We previously showed that cats that were infected with non-pathogenic Puma lentivirus (PLV) and then infected with pathogenic feline immunodeficiency virus (FIV) (co-infection with the host adapted/pathogenic virus) had delayed FIV proviral and RNA viral loads in blood, with viral set-points that were lower than cats infected solely with FIV. This difference was associated with global CD4⁺ T cell preservation, greater interferon gamma (IFN-γ) mRNA expression, and no cytotoxic T lymphocyte responses in co-infected cats relative to cats with a single FIV infection. In this study, we reinforced previous observations that prior exposure to an apathogenic lentivirus infection can diminish the effects of acute infection with a second, more virulent, viral exposure. In addition, we investigated whether the viral load differences that were observed between PLV/FIV and FIV infected cats were associated with different immunocyte phenotypes and cytokines. We found that the immune landscape at the time of FIV infection influences the infection outcome. The novel findings in this study advance our knowledge about early immune correlates and documents an immune state that is associated with PLV/FIV co-infection that has positive outcomes for lentiviral diseases. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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Review

Jump to: Research, Other

33 pages, 3352 KiB

Open AccessReview

Prospects in Innate Immune Responses as Potential Control Strategies against Non-Primate Lentiviruses

by Lorena De Pablo-Maiso, Ana Doménech, Irache Echeverría, Carmen Gómez-Arrebola, Damián De Andrés, Sergio Rosati, Esperanza Gómez-Lucia and Ramsés Reina

Viruses 2018, 10(8), 435; https://doi.org/10.3390/v10080435 - 17 Aug 2018

Cited by 17 | Viewed by 5936

Abstract

Lentiviruses are infectious agents of a number of animal species, including sheep, goats, horses, monkeys, cows, and cats, in addition to humans. As in the human case, the host immune response fails to control the establishment of chronic persistent infection that finally leads [...] Read more.

Lentiviruses are infectious agents of a number of animal species, including sheep, goats, horses, monkeys, cows, and cats, in addition to humans. As in the human case, the host immune response fails to control the establishment of chronic persistent infection that finally leads to a specific disease development. Despite intensive research on the development of lentivirus vaccines, it is still not clear which immune responses can protect against infection. Viral mutations resulting in escape from T-cell or antibody-mediated responses are the basis of the immune failure to control the infection. The innate immune response provides the first line of defense against viral infections in an antigen-independent manner. Antiviral innate responses are conducted by dendritic cells, macrophages, and natural killer cells, often targeted by lentiviruses, and intrinsic antiviral mechanisms exerted by all cells. Intrinsic responses depend on the recognition of the viral pathogen-associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs), and the signaling cascades leading to an antiviral state by inducing the expression of antiviral proteins, including restriction factors. This review describes the latest advances on innate immunity related to the infection by animal lentiviruses, centered on small ruminant lentiviruses (SRLV), equine infectious anemia virus (EIAV), and feline (FIV) and bovine immunodeficiency viruses (BIV), specifically focusing on the antiviral role of the major restriction factors described thus far. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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17 pages, 283 KiB

Open AccessReview

Non-Primate Lentiviral Vectors and Their Applications in Gene Therapy for Ocular Disorders

by Vincenzo Cavalieri, Elena Baiamonte and Melania Lo Iacono

Viruses 2018, 10(6), 316; https://doi.org/10.3390/v10060316 - 09 Jun 2018

Cited by 21 | Viewed by 4252

Abstract

Lentiviruses have a number of molecular features in common, starting with the ability to integrate their genetic material into the genome of non-dividing infected cells. A peculiar property of non-primate lentiviruses consists in their incapability to infect and induce diseases in humans, thus [...] Read more.

Lentiviruses have a number of molecular features in common, starting with the ability to integrate their genetic material into the genome of non-dividing infected cells. A peculiar property of non-primate lentiviruses consists in their incapability to infect and induce diseases in humans, thus providing the main rationale for deriving biologically safe lentiviral vectors for gene therapy applications. In this review, we first give an overview of non-primate lentiviruses, highlighting their common and distinctive molecular characteristics together with key concepts in the molecular biology of lentiviruses. We next examine the bioengineering strategies leading to the conversion of lentiviruses into recombinant lentiviral vectors, discussing their potential clinical applications in ophthalmological research. Finally, we highlight the invaluable role of animal organisms, including the emerging zebrafish model, in ocular gene therapy based on non-primate lentiviral vectors and in ophthalmology research and vision science in general. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

20 pages, 308 KiB

Open AccessReview

Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine

by Bikash Sahay and Janet K. Yamamoto

Viruses 2018, 10(5), 277; https://doi.org/10.3390/v10050277 - 22 May 2018

Cited by 10 | Viewed by 4512

Abstract

The feline immunodeficiency virus (FIV) vaccine called Fel-O-Vax^® FIV is the first commercial FIV vaccine released worldwide for the use in domestic cats against global FIV subtypes (A–E). This vaccine consists of inactivated dual-subtype (A plus D) FIV-infected cells, whereas its prototype [...] Read more.

The feline immunodeficiency virus (FIV) vaccine called Fel-O-Vax^® FIV is the first commercial FIV vaccine released worldwide for the use in domestic cats against global FIV subtypes (A–E). This vaccine consists of inactivated dual-subtype (A plus D) FIV-infected cells, whereas its prototype vaccine consists of inactivated dual-subtype whole viruses. Both vaccines in experimental trials conferred moderate-to-substantial protection against heterologous strains from homologous and heterologous subtypes. Importantly, a recent case-control field study of Fel-O-Vax-vaccinated cats with outdoor access and ≥3 years of annual vaccine boost, resulted in a vaccine efficacy of 56% in Australia where subtype-A viruses prevail. Remarkably, this protection rate is far better than the protection rate of 31.2% observed in the best HIV-1 vaccine (RV144) trial. Current review describes the findings from the commercial and prototype vaccine trials and compares their immune correlates of protection. The studies described in this review demonstrate the overarching importance of ant-FIV T-cell immunity more than anti-FIV antibody immunity in affording protection. Thus, future efforts in developing the next generation FIV vaccine and the first effective HIV-1 vaccine should consider incorporating highly conserved protective T-cell epitopes together with the conserved protective B-cell epitopes, but without inducing adverse factors that eliminate efficacy. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

16 pages, 1922 KiB

Open AccessReview

Properties and Functions of Feline Immunodeficiency Virus Gag Domains in Virion Assembly and Budding

by Silvia A. González and José L. Affranchino

Viruses 2018, 10(5), 261; https://doi.org/10.3390/v10050261 - 16 May 2018

Cited by 8 | Viewed by 3810

Abstract

Feline immunodeficiency virus (FIV) is an important cat pathogen worldwide whose biological and pathophysiological properties resemble those of human immunodeficiency virus type 1 (HIV-1). Therefore, the study of FIV not only benefits its natural host but is also useful for the development of [...] Read more.

Feline immunodeficiency virus (FIV) is an important cat pathogen worldwide whose biological and pathophysiological properties resemble those of human immunodeficiency virus type 1 (HIV-1). Therefore, the study of FIV not only benefits its natural host but is also useful for the development of antiviral strategies directed against HIV-1 infections in humans. FIV assembly results from the multimerization of a single but complex viral polypeptide, the Gag precursor. In this review, we will first give an overview of the current knowledge of the proteins encoded by the FIV pol, env, rev, vif, and orf-A genes, and then we will describe and discuss in detail the critical roles that each of the FIV Gag domains plays in virion morphogenesis. Since retroviral assembly is an attractive target for therapeutic interventions, gaining a better understanding of this process is highly desirable. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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23 pages, 1877 KiB

Open AccessReview

Epigenetic Modulation of CD8⁺ T Cell Function in Lentivirus Infections: A Review

by Mukta Nag, Kristina De Paris and Jonathan E. Fogle

Viruses 2018, 10(5), 227; https://doi.org/10.3390/v10050227 - 28 Apr 2018

Cited by 1 | Viewed by 5205

Abstract

CD8⁺ T cells are critical for controlling viremia during human immunodeficiency virus (HIV) infection. These cells produce cytolytic factors and antiviral cytokines that eliminate virally- infected cells. During the chronic phase of HIV infection, CD8⁺ T cells progressively lose their proliferative [...] Read more.

CD8⁺ T cells are critical for controlling viremia during human immunodeficiency virus (HIV) infection. These cells produce cytolytic factors and antiviral cytokines that eliminate virally- infected cells. During the chronic phase of HIV infection, CD8⁺ T cells progressively lose their proliferative capacity and antiviral functions. These dysfunctional cells are unable to clear the productively infected and reactivated cells, representing a roadblock in HIV cure. Therefore, mechanisms to understand CD8⁺ T cell dysfunction and strategies to boost CD8⁺ T cell function need to be investigated. Using the feline immunodeficiency virus (FIV) model for lentiviral persistence, we have demonstrated that CD8⁺ T cells exhibit epigenetic changes such as DNA demethylation during the course of infection as compared to uninfected cats. We have also demonstrated that lentivirus-activated CD4⁺CD25⁺ T regulatory cells induce forkhead box P3 (Foxp3) expression in virus-specific CD8⁺ T cell targets, which binds the interleukin (IL)-2, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ promoters in these CD8⁺ T cells. Finally, we have reported that epigenetic modulation reduces Foxp3 binding to these promoter regions. This review compares and contrasts our current understanding of CD8⁺ T cell epigenetics and mechanisms of lymphocyte suppression during the course of lentiviral infection for two animal models, FIV and simian immunodeficiency virus (SIV). Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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26 pages, 2393 KiB

Open AccessReview

Applications of the FIV Model to Study HIV Pathogenesis

by Craig Miller, Zaid Abdo, Aaron Ericsson, John Elder and Sue VandeWoude

Viruses 2018, 10(4), 206; https://doi.org/10.3390/v10040206 - 20 Apr 2018

Cited by 18 | Viewed by 8443

Abstract

Feline immunodeficiency virus (FIV) is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS). Much has been learned about FIV since it was first described in 1987, particularly in regard [...] Read more.

Feline immunodeficiency virus (FIV) is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS). Much has been learned about FIV since it was first described in 1987, particularly in regard to its application as a model to study the closely related lentivirus, human immunodeficiency virus (HIV). In particular, FIV and HIV share remarkable structure and sequence organization, utilize parallel modes of receptor-mediated entry, and result in a similar spectrum of immunodeficiency-related diseases due to analogous modes of immune dysfunction. This review summarizes current knowledge of FIV infection kinetics and the mechanisms of immune dysfunction in relation to opportunistic disease, specifically in regard to studying HIV pathogenesis. Furthermore, we present data that highlight changes in the oral microbiota and oral immune system during FIV infection, and outline the potential for the feline model of oral AIDS manifestations to elucidate pathogenic mechanisms of HIV-induced oral disease. Finally, we discuss advances in molecular biology, vaccine development, neurologic dysfunction, and the ability to apply pharmacologic interventions and sophisticated imaging technologies to study experimental and naturally occurring FIV, which provide an excellent, but often overlooked, resource for advancing therapies and the management of HIV/AIDS. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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16 pages, 16585 KiB

Open AccessReview

Feline APOBEC3s, Barriers to Cross-Species Transmission of FIV?

by Zeli Zhang, Qinyong Gu, Daniela Marino, Kyeong-Lim Lee, Il-Keun Kong, Dieter Häussinger and Carsten Münk

Viruses 2018, 10(4), 186; https://doi.org/10.3390/v10040186 - 10 Apr 2018

Cited by 7 | Viewed by 4887

Abstract

The replication of lentiviruses highly depends on host cellular factors, which defines their species-specific tropism. Cellular restriction factors that can inhibit lentiviral replication were recently identified. Feline immunodeficiency virus (FIV) was found to be sensitive to several feline cellular restriction factors, such as [...] Read more.

The replication of lentiviruses highly depends on host cellular factors, which defines their species-specific tropism. Cellular restriction factors that can inhibit lentiviral replication were recently identified. Feline immunodeficiency virus (FIV) was found to be sensitive to several feline cellular restriction factors, such as apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) and tetherin, but FIV evolved to counteract them. Here, we describe the molecular mechanisms by which feline APOBEC3 restriction factors inhibit FIV replication and discuss the molecular interaction of APOBEC3 proteins with the viral antagonizing protein Vif. We speculate that feline APOBEC3 proteins could explain some of the observed FIV cross-species transmissions described in wild Felids. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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Other

Jump to: Research, Review

8 pages, 335 KiB

Open AccessBrief Report

Absence of A3Z3-Related Hypermutations in the env and vif Proviral Genes in FIV Naturally Infected Cats

by Lucía Cano-Ortiz, Dennis Maletich Junqueira, Juliana Comerlato, André Zani, Cristina Santos Costa, Paulo Michel Roehe and Ana Cláudia Franco

Viruses 2018, 10(6), 296; https://doi.org/10.3390/v10060296 - 31 May 2018

Viewed by 2782

Abstract

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) proteins comprise an important family of restriction factors that produce hypermutations on proviral DNA and are able to limit virus replication. Vif, an accessory protein present in almost all lentiviruses, counteracts the antiviral A3 [...] Read more.

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) proteins comprise an important family of restriction factors that produce hypermutations on proviral DNA and are able to limit virus replication. Vif, an accessory protein present in almost all lentiviruses, counteracts the antiviral A3 activity. Seven haplotypes of APOBEC3Z3 (A3Z3) were described in domestic cats (hap I–VII), and in-vitro studies have demonstrated that these proteins reduce infectivity of vif-defective feline immunodeficiency virus (FIV). Moreover, hap V is resistant to vif-mediated degradation. However, studies on the effect of A3Z3 in FIV-infected cats have not been developed. Here, the correlation between APOBEC A3Z3 haplotypes in domestic cats and the frequency of hypermutations in the FIV vif and env genes were assessed in a retrospective cohort study with 30 blood samples collected between 2012 and 2016 from naturally FIV-infected cats in Brazil. The vif and env sequences were analyzed and displayed low or undetectable levels of hypermutations, and could not be associated with any specific A3Z3 haplotype. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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