scholarly journals Equine Infectious Anemia Virus Is Found in Tissue Macrophages during Subclinical Infection

1998 ◽  
Vol 72 (9) ◽  
pp. 7263-7269 ◽  
Author(s):  
J. Lindsay Oaks ◽  
Travis C. McGuire ◽  
Catherine Ulibarri ◽  
Timothy B. Crawford
Keyword(s):  
Viral Load ◽  
Viral Replication ◽  
Equine Infectious Anemia Virus ◽  
Disease Status ◽  
Viral Rna ◽  
Subclinical Infection ◽  
Equine Infectious Anemia ◽  
Infected Cells ◽  
Anemia Virus

ABSTRACT The equine infectious anemia virus (EIAV) often results in lifelong subclinical infection following early episodes of clinical disease. To identify the cellular reservoirs of EIAV during subclinical infection, horses were infected with EIAV and allowed to develop subclinical infections. Horses with acute disease served as a basis for comparison. The tissue distribution, replication status, location of infected cells, and viral load were characterized by PCR for proviral DNA and reverse transcriptase PCR for viral RNA, in situ hybridization, and in situ PCR. Proviral DNA was widespread in tissues regardless of disease status. Viral gag and env RNAs were also detected in tissues of all horses regardless of disease status. Plasma viral RNA (viremia) could be detected in some, but not all, horses with subclinical infections. In situ assays determined that a primary cellular reservoir and site of viral replication during subclinical infection is the macrophage. During subclinical infection, viral load was decreased 4- to 733-fold and there was decreased viral RNA expression within infected cells. These data indicate that viral replication continues at all times, even in horses that are clinically quiescent. Moreover, restricted viral replication at the cellular level is associated with clinical remission.

scholarly journals A Particulate Viral Protein Vaccine Reduces Viral Load and Delays Progression to Disease in Immunized Ponies Challenged with Equine Infectious Anemia Virus

Virology ◽  
1999 ◽  
Vol 254 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Scott A. Hammond ◽  
Sheila J. Cook ◽  
Louis D. Falo ◽  
Charles J. Issel ◽  
Ronald C. Montelaro
Keyword(s):  
Viral Load ◽  
Viral Protein ◽  
Equine Infectious Anemia Virus ◽  
Protein Vaccine ◽  
Equine Infectious Anemia ◽  
Anemia Virus

scholarly journals Mutation of YMYL in the Nipah Virus Matrix Protein Abrogates Budding and Alters Subcellular Localization

2006 ◽  
Vol 80 (24) ◽  
pp. 12070-12078 ◽  
Author(s):  
Michael J. Ciancanelli ◽  
Christopher F. Basler
Keyword(s):  
Matrix Protein ◽  
Ebola Virus ◽  
Equine Infectious Anemia Virus ◽  
Nipah Virus ◽  
Gag Protein ◽  
Late Domain ◽  
M Proteins ◽  
Equine Infectious Anemia ◽  
Infected Cells ◽  
Anemia Virus

ABSTRACT Matrix (M) proteins reportedly direct the budding of paramyxoviruses from infected cells. In order to begin to characterize the assembly process for the highly lethal, emerging paramyxovirus Nipah virus (NiV), we have examined the budding of NiV M. We demonstrated that expression of the NiV M protein is sufficient to produce budding virus-like particles (VLPs) that are physically and morphologically similar to NiV. We identified in NiV M a sequence, YMYL, with similarity to the YPDL late domain found in the equine infectious anemia virus Gag protein. When the YMYL within NiV M was mutated, VLP release was abolished and M was relocalized to the nucleus, but the mutant M proteins retained oligomerization activity. When YMYL was fused to a late-domain mutant of the Ebola virus VP40 matrix protein, VP40 budding was restored. These results suggest that the YMYL sequence may act as a trafficking signal and a late domain for NiV M.

scholarly journals An Equine Infectious Anemia Virus Variant Superinfects Cells through Novel Receptor Interactions

2008 ◽  
Vol 82 (19) ◽  
pp. 9425-9432 ◽  
Author(s):  
Melinda A. Brindley ◽  
Baoshan Zhang ◽  
Ronald C. Montelaro ◽  
Wendy Maury
Keyword(s):  
Endothelial Cells ◽  
Equine Infectious Anemia Virus ◽  
Cell Monolayer ◽  
Wild Type ◽  
Virus Variant ◽  
Receptor Interactions ◽  
Equine Infectious Anemia ◽  
Infected Cells ◽  
Anemia Virus ◽  
Type Strains

ABSTRACT Wild-type strains of equine infectious anemia virus (EIAV) prevent superinfection of previously infected cells. A variant strain of virus that spontaneously arose during passage, EIAVvMA-1c, can circumvent this mechanism in some cells, such as equine dermis (ED) cells, but not in others, such as equine endothelial cells. EIAVvMA-1c superinfection of ED cells results in a buildup of unintegrated viral DNA and rapid killing of the cell monolayer. Here, we examined the mechanism of resistance that is used by EIAV to prevent superinfection and explored the means by which EIAVvMA-1c overcomes this restriction. We found that the cellular receptor used by EIAV, equine lentivirus receptor 1 (ELR1), remains on the surface of cells chronically infected with EIAV, suggesting that wild-type EIAV interferes with superinfection by masking ELR1. The addition of soluble wild-type SU protein to the medium during infection blocked infection by wild-type strains of virus, implicating SU as the viral protein responsible for interfering with virion entry into previously infected cells. Additionally, interference of wild-type EIAV binding to ELR1 by the addition of either anti-ELR1 antibodies or the ELR1 ectodomain prevented entry of the wild-type strains of EIAV into two permissive cell populations. Many of these same interference treatments prevented EIAVvMA-1c infection of endothelial cells but only modestly affected the ability of EIAVvMA-1c to enter and kill previously infected ED cells. These findings indicate that EIAVvMA-1c retains the ability to use ELR1 for entry and suggest that this virus can interact with an additional, unidentified receptor to superinfect ED cells.

scholarly journals Equine Infectious Anemia Virus and the Ubiquitin-Proteasome System

2002 ◽  
Vol 76 (6) ◽  
pp. 3038-3044 ◽  
Author(s):  
David E. Ott ◽  
Lori V. Coren ◽  
Raymond C. Sowder ◽  
Julian Adams ◽  
Kunio Nagashima ◽  
...  
Keyword(s):  
Time Course ◽  
Equine Infectious Anemia Virus ◽  
Proteasome Inhibitors ◽  
Ubiquitin Proteasome System ◽  
Gag Protein ◽  
Different Types ◽  
Ubiquitin Proteasome ◽  
Equine Infectious Anemia ◽  
Infected Cells ◽  
Anemia Virus

ABSTRACT Some retroviruses contain monoubiquitinated Gag and do not bud efficiently from cells treated with proteasome inhibitors, suggesting an interaction between the ubiquitin-proteasome system and retrovirus assembly. We examined equine infectious anemia virus (EIAV) particles and found that approximately 2% of the p9Gag proteins are monoubiquitinated, demonstrating that this Gag protein interacts with an ubiquitinating activity. Different types of proteasome inhibitors were used to determine if proteasome inactivation affects EIAV release from chronically infected cells. Pulse-chase immunoprecipitation and time course immunoblot analyses showed that proteasome inactivation slightly decreased virus release (at most a twofold effect), while it did not affect Gag processing. These results contrast with those obtained with other viruses which are sensitive to these inhibitors. This suggests that, although its Gag is monoubiquitinated, the requirements for EIAV release are somewhat different from those for retroviruses that are sensitive to proteasome inhibitors.

scholarly journals Differential Effects of Actin Cytoskeleton Dynamics on Equine Infectious Anemia Virus Particle Production

2004 ◽  
Vol 78 (2) ◽  
pp. 882-891 ◽  
Author(s):  
Chaoping Chen ◽  
Ora A. Weisz ◽  
Donna B. Stolz ◽  
Simon C. Watkins ◽  
Ronald C. Montelaro
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Filaments ◽  
Equine Infectious Anemia Virus ◽  
Cytochalasin D ◽  
Full Length ◽  
Gag Proteins ◽  
Virion Production ◽  
Equine Infectious Anemia ◽  
Infected Cells ◽  
Anemia Virus

ABSTRACT Retrovirus assembly and budding involve a highly dynamic and concerted interaction of viral and cellular proteins. Previous studies have shown that retroviral Gag proteins interact with actin filaments, but the significance of these interactions remains to be defined. Using equine infectious anemia virus (EIAV), we now demonstrate differential effects of cellular actin dynamics at distinct stages of retrovirus assembly and budding. First, virion production was reduced when EIAV-infected cells were treated with phallacidin, a cell-permeable reagent that stabilizes actin filaments by slowing down their depolymerization. Confocal microscopy confirmed that the inhibition of EIAV production correlated temporally over several days with the incorporation dynamics of phallacidin into the actin cytoskeleton. Although the overall structure of the actin cytoskeleton and expression of viral protein appeared to be unaffected, phallacidin treatment dramatically reduced the amount of full-length Gag protein associated with the actin cytoskeleton. These data suggest that an association of full-length Gag proteins with de novo actin filaments might contribute to Gag assembly and budding. On the other hand, virion production was enhanced when EIAV-infected cells were incubated briefly (2 h) with the actin-depolymerizing drugs cytochalasin D and latrunculin B. Interestingly, the enhanced virion production induced by cytochalasin D required a functional late (L) domain, either the EIAV YPDL L-domain or the proline-rich L domains derived from human immunodeficiency virus type 1 or Rous sarcoma virus, respectively. Thus, depolymerization of actin filaments may be a common function mediated by retrovirus L domains during late stages of viral budding. Taken together, these observations indicate that dynamic actin polymerization and depolymerization may be associated with different stages of viral production.

scholarly journals The S2 Gene of Equine Infectious Anemia Virus Is a Highly Conserved Determinant of Viral Replication and Virulence Properties in Experimentally Infected Ponies

2000 ◽  
Vol 74 (1) ◽  
pp. 573-579 ◽  
Author(s):  
Feng Li ◽  
Caroline Leroux ◽  
Jodi K. Craigo ◽  
Sheila J. Cook ◽  
Charles J. Issel ◽  
...  
Keyword(s):  
Viral Replication ◽  
Equine Infectious Anemia Virus ◽  
Parental Virus ◽  
In Vivo Studies ◽  
Viral Gene ◽  
Viral Virulence ◽  
Equine Infectious Anemia ◽  
Anemia Virus

ABSTRACT Equine infectious anemia virus (EIAV) is genetically one of the simplest lentiviruses in that the viral genome encodes only three accessory genes, tat, rev, and S2. Although serological analyses demonstrate the expression of the S2 protein in persistently infected horses, the role of this viral gene remains undefined. We recently reported that the S2 gene is not essential for EIAV replication in primary equine macrophages, as EIAV mutants lacking the S2 gene replicate to levels similar to those of the parental virus (F. Li, B. A. Puffer, and R. C. Montelaro, J. Virol. 72:8344–8348, 1998). We now describe in vivo studies that examine the evolution and role of theS2 gene in ponies experimentally infected with EIAV. The results of these studies reveal for the first time that theS2 gene is highly conserved during persistent infection and that deletion of the S2 gene reduces viral virulence and virus replication levels compared to those of the parental virus containing a functional S2 gene. These data indicate that the EIAV S2 gene is in fact an important determinant of viral replication and pathogenic properties in vivo, despite the evident lack of S2 influence on viral replication levels in vitro. Thus, these observations suggest in vivo functions of EIAVS2 that are not adequately reflected in simple infections of cultured cells, including natural target macrophages.

scholarly journals Equine Infectious Anemia Virus Genomic Evolution in Progressor and Nonprogressor Ponies

2001 ◽  
Vol 75 (10) ◽  
pp. 4570-4583 ◽  
Author(s):  
Caroline Leroux ◽  
Jodi K. Craigo ◽  
Charles J. Issel ◽  
Ronald C. Montelaro
Keyword(s):  
Steady State ◽  
Viral Replication ◽  
Virus Replication ◽  
Equine Infectious Anemia Virus ◽  
Genomic Rna ◽  
Equine Infectious Anemia ◽  
Steady State Levels ◽  
Anemia Virus ◽  
First Time

ABSTRACT A primary mechanism of lentivirus persistence is the ability of these viruses to evolve in response to biological and immunological selective pressures with a remarkable array of genetic and antigenic variations that constitute a perpetual natural experiment in genetic engineering. A widely accepted paradigm of lentivirus evolution is that the rate of genetic variation is correlated directly with the levels of virus replication: the greater the viral replication, the more opportunities that exist for genetic modifications and selection of viral variants. To test this hypothesis directly, we examined the patterns of equine infectious anemia virus (EIAV) envelope variation during a 2.5-year period in experimentally infected ponies that differed markedly in clinical progression and in steady-state levels of viral replication as indicated by plasma virus genomic RNA assays. The results of these comprehensive studies revealed for the first time similar extents of envelope gp90 variation in persistently infected ponies regardless of the number of disease cycles (one to six) and viremia during chronic disease. The extent of envelope variation was also independent of the apparent steady-state levels of virus replication during long-term asymptomatic infection, varying from undetectable to 105 genomic RNA copies per ml of plasma. In addition, the data confirmed the evolution of distinct virus populations (genomic quasispecies) associated with sequential febrile episodes during acute and chronic EIA and demonstrated for the first time ongoing envelope variation during long-term asymptomatic infections. Finally, comparison of the rates of evolution of the previously defined EIAV gp90 variable domains demonstrated distinct differences in the rates of nucleotide and amino acid sequence variation, presumably reflecting differences in the ability of different envelope domains to respond to immune or other biological selection pressures. Thus, these data suggest that EIAV variation can be associated predominantly with ongoing low levels of virus replication and selection in target tissues, even in the absence of substantial levels of plasma viremia, and that envelope variation continues during all stages of persistent infection as the virus successfully avoids clearance by host defense mechanisms.

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