Mechanisms of retroviral replication

2001 ◽  
Author(s):  
Timur O. Kabdulov
Keyword(s):  
Retroviral Replication

scholarly journals Persistence of Viremia and Production of Neutralizing Antibodies Differentially Regulated by Polymorphic APOBEC3 and BAFF-R Loci in Friend Virus-Infected Mice

2010 ◽  
Vol 84 (12) ◽  
pp. 6082-6095 ◽  
Author(s):  
Sachiyo Tsuji-Kawahara ◽  
Tomomi Chikaishi ◽  
Eri Takeda ◽  
Maiko Kato ◽  
Saori Kinoshita ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Early Stage ◽  
Chromosome 15 ◽  
Cell Repertoire ◽  
Viral Loads ◽  
Functional Polymorphisms ◽  
B Cell Repertoire ◽  
Retroviral Replication ◽  
Different Strains ◽  
Host Genes

ABSTRACT Several host genes control retroviral replication and pathogenesis through the regulation of immune responses to viral antigens. The Rfv3 gene influences the persistence of viremia and production of virus-neutralizing antibodies in mice infected with Friend mouse retrovirus complex (FV). This locus has been mapped within a narrow segment of mouse chromosome 15 harboring the APOBEC3 and BAFF-R loci, both of which show functional polymorphisms among different strains of mice. The exon 5-lacking product of the APOBEC3 allele expressed in FV-resistant C57BL/6 (B6) mice directly restricts viral replication, and mice lacking the B6-derived APOBEC3 exhibit exaggerated pathology and reduced production of neutralizing antibodies. However, the mechanisms by which the polymorphisms at the APOBEC3 locus affect the production of neutralizing antibodies remain unclear. Here we show that the APOBEC3 genotypes do not directly affect the B-cell repertoire, and mice lacking B6-derived APOBEC3 still produce FV-neutralizing antibodies in the presence of primed T helper cells. Instead, higher viral loads at a very early stage of FV infection caused by either a lack of the B6-derived APOBEC3 or a lack of the wild-type BAFF-R resulted in slower production of neutralizing antibodies. Indeed, B cells were hyperactivated soon after infection in the APOBEC3- or BAFF-R-deficient mice. In contrast to mice deficient in the B6-derived APOBEC3, which cleared viremia by 4 weeks after FV infection, mice lacking the functional BAFF-R allele exhibited sustained viremia, indicating that the polymorphisms at the BAFF-R locus may better explain the Rfv3-defining phenotype of persistent viremia.

scholarly journals Isolation of Cell Lines That Show Novel, Murine Leukemia Virus-Specific Blocks to Early Steps of Retroviral Replication

2005 ◽  
Vol 79 (20) ◽  
pp. 12969-12978 ◽  
Author(s):  
James W. Bruce ◽  
Kenneth A. Bradley ◽  
Paul Ahlquist ◽  
John A. T. Young
Keyword(s):  
Cell Lines ◽  
Reverse Transcription ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Mutant Cell ◽  
Chinese Hamster ◽  
High Volume ◽  
Early Stages ◽  
Retroviral Replication ◽  
Murine Leukemia

ABSTRACT In order to identify cellular proteins required for early stages of retroviral replication, a high volume screening with mammalian somatic cells was performed. Ten pools of chemically mutagenized Chinese hamster ovary (CHO-K1) cells were challenged with a murine leukemia virus (MLV) vector pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G), and cells that failed to be transduced were enriched by cell sorting. Each pool yielded a clonally derived cell line with a 5-fold or greater resistance to virus infection, and five cell lines exhibited a >50-fold resistance. These five cell lines were efficiently infected by a human immunodeficiency virus vector pseudotyped with VSV-G. When engineered to express the TVA receptor for subgroup A avian sarcoma and leukosis virus (ASLV-A), the five cell lines were resistant to infection with a MLV vector pseudotyped with the ASLV-A envelope protein but were fully susceptible to infection with an ASLV-A vector. Thus, the defect in these cells resides after virus-cell membrane fusion and, unlike those in other mutant cell lines that have been described, is specific for the MLV core. To identify the specific stages of MLV infection that are impaired in the resistant cell lines, real-time quantitative PCR analyses were employed and two phenotypic groups were identified. Viral infection of three cell lines was restricted before reverse transcription; in the other two cell lines, it was blocked after reverse transcription, nuclear localization, and two-long terminal repeat circle formation but before integration. These data provide genetic evidence that at least two distinct intracellular gene products are required specifically for MLV infection. These cell lines are important tools for the biochemical and genetic analysis of early stages in retrovirus infection.

Inhibition of retroviral replication by anti-sense RNA

1986 ◽  
Vol 6 (12) ◽  
pp. 4758-4762
Author(s):  
R Y To ◽  
S C Booth ◽  
P E Neiman
Keyword(s):  
Steady State ◽  
Cultured Cells ◽  
Host Cells ◽  
Rna Molecules ◽  
Sense Orientation ◽  
Steady State Levels ◽  
Rna Inhibition ◽  
Retroviral Replication ◽  
Retroviral Infections ◽  
Neomycin Resistance

We tested the effect of anti-sense RNA on the replication of avian retroviruses in cultured cells. The replication of a recombinant retrovirus carrying a neomycin resistance gene (neor) in the anti-sense orientation was blocked when the cells expressed high steady-state levels of RNA molecules with neor in sequence in the sense was blocked when the cells expressed high steady-state levels of RNA molecules with neor sequences in the sense orientation, i.e., complementary to the viral sequence. Viral DNA bearing neor sequences was not detected specifically in host cells where this anti-sense RNA inhibition of viral replication occurred. These observations suggest that anti-sense RNA inhibition may be a useful strategy for the inhibition of retroviral infections.

Retroviral Replication

2003 ◽  
Author(s):  
Finn Skou Pedersen ◽  
Mogens Duch
Keyword(s):  
Retroviral Replication

scholarly journals The Raft-Promoting Property of Virion-Associated Cholesterol, but Not the Presence of Virion-Associated Brij 98 Rafts, Is a Determinant of Human Immunodeficiency Virus Type 1 Infectivity

2004 ◽  
Vol 78 (19) ◽  
pp. 10556-10565 ◽  
Author(s):  
Shahan Campbell ◽  
Katharina Gaus ◽  
Robert Bittman ◽  
Wendy Jessup ◽  
Suzanne Crowe ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Hiv Replication ◽  
Exogenous Cholesterol ◽  
Immunodeficiency Virus ◽  
Retroviral Replication ◽  
Triton X ◽  
Hiv 1

ABSTRACT Lipid rafts are enriched in cholesterol and sphingomyelin and are isolated on the basis of insolubility in detergents, such as Brij 98 and Triton X-100. Recent work by Holm et al. has shown that rafts insoluble in Brig 98 can be found in human immunodeficiency virus type 1 (HIV-1) virus-like particles, although it is not known whether raft-like structures are present in authentic HIV-1 and it is unclear whether a virion-associated raft-like structure is required for HIV replication. Independently, it was previously reported that virion-associated cholesterol is critical for HIV-1 infectivity, although the specific requirement of virion cholesterol in HIV-1 was not examined. In the present study, we have demonstrated that infectious wild-type HIV-1 contains Brij 98 rafts but only minimal amounts of Triton X-100 rafts. To directly assess the functional requirement of virion-associated rafts and various features of cholesterol on HIV-1 replication, we replaced virion cholesterol with exogenous cholesterol analogues that have demonstrated either raft-promoting or -inhibiting capacity in model membranes. We observed that variable concentrations of exogenous analogues are required to replace a defined amount of virion-associated cholesterol, showing that structurally diverse cholesterol analogues have various affinities toward HIV-1. We found that replacement of 50% of virion cholesterol with these exogenous cholesterol analogues did not eliminate the presence of Brij 98 rafts in HIV-1. However, the infectivity levels of the lipid-modified HIV-1s directly correlate with the raft-promoting capacities of these cholesterol analogues. Our data provide the first direct assessment of virion-associated Brij 98 rafts in retroviral replication and illustrate the importance of the raft-promoting property of virion-associated cholesterol in HIV-1 replication.

scholarly journals Retroviral vector system for the study of cDNA gene formation.

1988 ◽  
Vol 8 (6) ◽  
pp. 2328-2334 ◽  
Author(s):  
R Dornburg ◽  
H M Temin
Keyword(s):  
Southern Blot ◽  
Blot Analysis ◽  
Southern Blot Analysis ◽  
Retroviral Vector ◽  
Vector System ◽  
Cis Acting ◽  
Infected Cells ◽  
Retroviral Replication

A retroviral vector system was developed to study the retrotransposition of RNAs lacking all cis-acting sequences required for normal retroviral replication. Our experiments indicate that such RNAs can be encapsidated in retroviral proteins, reverse transcribed, and integrated to form functional cDNA genes in infected cells. The frequency of this process, however, was approximately 8 orders of magnitude less than that of normal retroviral replication. The efficiency was limited at each step in this process. Investigation of seven cDNA genes by Southern blot analysis revealed that all of them were truncated at either the 3' or the 5' end or both. These truncations are not seen with natural cDNA genes and raise the question of retroviral involvement in their formation.

scholarly journals Mouse APOBEC3 affects the production of virus-neutralizing antibodies by restricting early retroviral replication, not by altering the B-cell repertoire

Retrovirology ◽  
2009 ◽  
Vol 6 (S2) ◽  
Author(s):  
Masaaki Miyazawa ◽  
Sachiyo Tsuji-Kawahara ◽  
Tomomi Chikaishi ◽  
Maiko Kato ◽  
Shiki Takamura
Keyword(s):  
B Cell ◽  
Neutralizing Antibodies ◽  
Cell Repertoire ◽  
B Cell Repertoire ◽  
Retroviral Replication
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