Contribution of Glutamine Residues in the Helix 4-5 Loop to Capsid-Capsid Interactions in Simian Immunodeficiency Virus of Macaques
| Autor: | Christopher H. Tipper, Joseph Sodroski |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Glutamine
viruses Amino Acid Motifs Molecular Sequence Data Immunology Simian Acquired Immunodeficiency Syndrome HIV Infections Cypa Plasma protein binding medicine.disease_cause Microbiology Protein Structure Secondary Virus Capsid Retrovirus Virology medicine Animals Humans Amino Acid Sequence Peptide sequence biology Structure and Assembly Simian immunodeficiency virus biology.organism_classification Insect Science HIV-1 Macaca Capsid Proteins Simian Immunodeficiency Virus Cyclophilin A Sequence Alignment Protein Binding |
| Zdroj: | Journal of Virology. 88:10289-10302 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Following retrovirus entry, the viral capsid (CA) disassembles into its component capsid proteins. The rate of this uncoating process, which is regulated by CA-CA interactions and by the association of the capsid with host cell factors like cyclophilin A (CypA), can influence the efficiency of reverse transcription. Inspection of the CA sequences of lentiviruses reveals that several species of simian immunodeficiency viruses (SIVs) have lost the glycine-proline motif in the helix 4-5 loop important for CypA binding; instead, the helix 4-5 loop in these SIVs exhibits an increase in the number of glutamine residues. In this study, we investigated the role of these glutamine residues in SIVmac239 replication. Changes in these residues, particularly glutamine 89 and glutamine 92, resulted in a decreased efficiency of core condensation, decreased stability of the capsids in infected cells, and blocks to reverse transcription. In some cases, coexpression of two different CA mutants produced chimeric virions that exhibited higher infectivity than either parental mutant virus. For this complementation of infectivity, glutamine 89 was apparently required on one of the complementing pair of mutants and glutamine 92 on the other. Modeling suggests that glutamines 89 and 92 are located on the distal face of hexameric capsid spokes and thus are well positioned to contribute to interhexamer interactions. Requirements to evade host restriction factors like TRIMCyp may drive some SIV lineages to evolve means other than CypA binding to stabilize the capsid. One solution used by several SIV strains consists of glutamine-based bonding. IMPORTANCE The retroviral capsid is an assembly of individual capsid proteins that surrounds the viral RNA. After a retrovirus enters a cell, the capsid must disassemble, or uncoat, at a proper rate. The interactions among capsid proteins contribute to this rate of uncoating. We found that some simian immunodeficiency viruses use arrays of glutamine residues, which can form hydrogen bonds efficiently, to keep their capsids stable. This strategy may allow these viruses to forego the use of capsid-stabilizing factors from the host cell, some of which have antiviral activity. |
| Databáze: | OpenAIRE |
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