HIV Mutation Detail Information

Virus Mutation HIV Mutation P90D


Basic Characteristics of Mutations
Mutation Site P90D
Mutation Site Sentence This variant, called the RGDA/Q112D virus, contains multiple mutations in CA: H87R, A88G, P90D, P93A, and Q112D.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region CA
Standardized Encoding Gene Gag  
Genotype/Subtype HIV-1
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment IFN-beta
Location -
Literature Information
PMID 31511380
Title Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid
Author Sultana T,Mamede JI,Saito A,Ode H,Nohata K,Cohen R,Nakayama EE,Iwatani Y,Yamashita M,Hope TJ,Shioda T
Journal Journal of virology
Journal Info 2019 Nov 13;93(23):e00986-19
Abstract Type I interferons (IFNs), including alpha IFN (IFN-alpha) and IFN-beta, potently suppress HIV-1 replication by upregulating IFN-stimulated genes (ISGs). The viral capsid protein (CA) partly determines the sensitivity of HIV-1 to IFNs. However, it remains to be determined whether CA-related functions, including utilization of known host factors, reverse transcription, and uncoating, affect the sensitivity of HIV-1 to IFN-mediated restriction. Recently, we identified an HIV-1 CA variant that is unusually sensitive to IFNs. This variant, called the RGDA/Q112D virus, contains multiple mutations in CA: H87R, A88G, P90D, P93A, and Q112D. To investigate how an IFN-hypersensitive virus can evolve to overcome IFN-beta-mediated blocks targeting the viral capsid, we adapted the RGDA/Q112D virus in IFN-beta-treated cells. We successfully isolated IFN-beta-resistant viruses which contained either a single Q4R substitution or the double amino acid change G94D/G116R. These two IFN-beta resistance mutations variably changed the sensitivity of CA binding to human myxovirus resistance B (MxB), cleavage and polyadenylation specificity factor 6 (CPSF6), and cyclophilin A (CypA), indicating that the observed loss of sensitivity was not due to interactions with these known host CA-interacting factors. In contrast, the two mutations apparently functioned through distinct mechanisms. The Q4R mutation dramatically accelerated the kinetics of reverse transcription and initiation of uncoating of the RGDA/Q112D virus in the presence or absence of IFN-beta, whereas the G94D/G116R mutations affected reverse transcription only in the presence of IFN-beta, most consistent with a mechanism of the disruption of binding to an unknown IFN-beta-regulated host factor. These results suggest that HIV-1 can exploit multiple, known host factor-independent pathways to avoid IFN-beta-mediated restriction by altering capsid sequences and subsequent biological properties.IMPORTANCE HIV-1 infection causes robust innate immune activation in virus-infected patients. This immune activation is characterized by elevated levels of type I interferons (IFNs), which can block HIV-1 replication. Recent studies suggest that the viral capsid protein (CA) is a determinant for the sensitivity of HIV-1 to IFN-mediated restriction. Specifically, it was reported that the loss of CA interactions with CPSF6 or CypA leads to higher IFN sensitivity. However, the molecular mechanism of CA adaptation to IFN sensitivity is largely unknown. Here, we experimentally evolved an IFN-beta-hypersensitive CA mutant which showed decreased binding to CPSF6 and CypA in IFN-beta-treated cells. The CA mutations that emerged from this adaptation indeed conferred IFN-beta resistance. Our genetic assays suggest a limited contribution of known host factors to IFN-beta resistance. Strikingly, one of these mutations accelerated the kinetics of reverse transcription and uncoating. Our findings suggest that HIV-1 selected multiple, known host factor-independent pathways to avoid IFN-beta-mediated restriction.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.