Identification of a new 2‐amino acid insertion in the integrase coding region of HIV‐1 subtype G isolates

2021 ◽  
Author(s):  
João Pereira‐Vaz ◽  
Pedro Crespo ◽  
Luísa Mocho ◽  
Patrícia Martinho ◽  
Teresa Fidalgo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Coding Region ◽  
Amino Acid Insertion ◽  
Hiv 1

scholarly journals Effects of the Δ67 Complex of Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase on Nucleoside Analog Excision

2004 ◽  
Vol 78 (18) ◽  
pp. 9987-9997 ◽  
Author(s):  
Paul L. Boyer ◽  
Tomozumi Imamichi ◽  
Stefan G. Sarafianos ◽  
Edward Arnold ◽  
Stephen H. Hughes
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Amino Acid Substitutions ◽  
Wild Type ◽  
Coding Region ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Long-term use of combination therapy against human immunodeficiency virus type (HIV-1) provides strong selective pressure on the virus, and HIV-1 variants that are resistant to multiple inhibitors have been isolated. HIV-1 variants containing amino acid substitutions within the coding region of HIV-1 reverse transcriptase (RT), such as the 3′-azido-3′-deoxythymidine (AZT)-resistant variant AZT-R (M41L/D67N/K70R/T215Y/K219Q) and a variant containing an insertion in the fingers domain (S69SGR70/T215Y), are resistant to the nucleoside RT inhibitor (NRTI) AZT because of an increase in the level of excision of AZT monophosphate (AZTMP) from the primer. While rare, variants have also been isolated which contain deletions in the RT coding region. One such virus, described by Imamichi et al. (J. Virol 74:10958-10964, 2000; J. Virol. 74:1023-1028, 2000; J. Virol. 75:3988-3992, 2001), contains numerous amino acid substitutions and a deletion of codon 67, which we have designated the Δ67 complex of mutations. We have expressed and purified HIV-1 RT containing these mutations. We compared the polymerase and pyrophosphorolysis (excision) activity of an RT with the Δ67 complex of mutations to wild-type RT and the two other AZT-resistant variants described above. All of the AZT-resistant variants we tested excise AZTMP and 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA [tenofovir]) from the end of a primer more efficiently than wild-type RT. Although the variant RTs excised d4TMP less efficiently than AZTMP and PMPA, they were able to excise d4TMP more efficiently than wild-type RT. HIV-1 RT containing the Δ67 complex of mutations was not able to excise as broad a range of NRTIs as the fingers insertion variant SSGR/T215Y, but it was able to polymerize efficiently with low concentrations of deoxynucleoside triphosphates and seems to be able to excise AZTMP and PMPA at lower ATP concentrations than AZT-R or SSGR/T215Y, suggesting that a virus containing the Δ67 complex of mutations would replicate reasonably well in quiescent cells, even in the presence of AZT.

scholarly journals Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Replication by a Two-Amino-Acid Insertion in HIV-1 Vif from a Nonprogressing Mother and Child

2002 ◽  
Vol 76 (20) ◽  
pp. 10533-10539 ◽  
Author(s):  
Louis Alexander ◽  
Mary Janette Aquino-DeJesus ◽  
Michael Chan ◽  
Warren A. Andiman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Human Immunodeficiency Virus Type ◽  
Insertion Mutation ◽  
Wild Type ◽  
Amino Acid Insertion ◽  
Immunodeficiency Virus ◽  
Mother And Child ◽  
Hiv 1

ABSTRACT We studied a 15-year-old girl, patient X, who has maintained consistently low plasma loads of human immunodeficiency virus type 1 (HIV-1) RNA, as well as normal and stable CD4+ T-cell concentrations. She has presented no clinical manifestations of AIDS, despite having only received zidovudine monotherapy for a part of her life. Patient X's HIV-positive mother (patient Y) has also not progressed to AIDS and has never been treated with antiretroviral agents. HIV-1 isolated from patient X replicated poorly in human peripheral blood mononuclear cells (PBMC). In order to map the determinant of the poor growth of patient X's isolate, viral sequences from patient X were determined and examined for insertion or deletion mutations. These sequences contained a two-amino-acid insertion mutation in the Vif gene, which was also observed in uncultured PBMC acquired at different times. Furthermore, Vif sequences harbored by patient Y contained the identical mutation. These observations suggest that polymorphic HIV-1 was transmitted to patient X perinatally 15 years previously and has been maintained since that time. Recombinant HIV-1, engineered with Vif sequences from patient X, replicated in PBMC to levels approximately 20-fold lower than that of wild type. Removal of the insertion mutation from this recombinant restored replication efficiency to wild-type levels, while introduction of the insertion mutation into wild-type Vif sequences resulted in greatly decreased replication. Furthermore, Vif protein from patient X's HIV-1 was aberrantly cleaved, suggesting a mechanism for loss of Vif function. Since HIV-1 containing these sequences replicates poorly, the implication is that the two-amino-acid insertion mutation in Vif contributes significantly to the nonprogressor status of this mother and child. Further studies of these sequences might provide information regarding contributions of Vif structure and/or function to HIV-1 virulence.

scholarly journals Evolution of a novel 5-amino-acid insertion in the β3–β4 loop of HIV-1 reverse transcriptase

Virology ◽  
2007 ◽  
Vol 364 (2) ◽  
pp. 395-406 ◽  
Author(s):  
Marleen C.D.G. Huigen ◽  
Loek de Graaf ◽  
Dirk Eggink ◽  
Rob Schuurman ◽  
Viktor Müller ◽  
...  
Keyword(s):  
Amino Acid ◽  
Reverse Transcriptase ◽  
Amino Acid Insertion ◽  
Hiv 1

scholarly journals Detection of the protease codon 35 amino acid insertion in sequences from treatment-naïve HIV-1 subtype C infected individuals in the Central Region of Portugal

2009 ◽  
Vol 46 (2) ◽  
pp. 169-172 ◽  
Author(s):  
João Pereira-Vaz ◽  
Vitor Duque ◽  
Luís Trindade ◽  
José Saraiva-da-Cunha ◽  
António Meliço-Silvestre
Keyword(s):  
Amino Acid ◽  
Central Region ◽  
Subtype C ◽  
Amino Acid Insertion ◽  
Treatment Naïve ◽  
Hiv 1

scholarly journals Influence of codon 35 amino acid insertion in HIV-1 protease: insights from molecular dynamics

2018 ◽  
Author(s):  
João Luís ◽  
Ana Mata ◽  
Nuno Alves ◽  
Carlos Simões ◽  
João Pereira-Vaz ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Amino Acid Insertion ◽  
Hiv 1

scholarly journals A first case of protease codon 35 amino acid insertion in a HIV-1 subtype B sequence detected in the Bauru region, state of São Paulo, Brazil: case report

2011 ◽  
Vol 44 (3) ◽  
pp. 392-394
Author(s):  
Rejane Maria Tommasini Grotto ◽  
Sílvia Maria Corvino ◽  
Lilian da Silva Reis Munhoz ◽  
Cibele Gomes Ghedini ◽  
Maria Inês de Moura Campos Pardini
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Sao Paulo ◽  
São Paulo ◽  
Subtype B ◽  
Amino Acid Insertion ◽  
First Case ◽  
First Time ◽  
Hiv 1 ◽  
Asymptomatic Hiv

Amino acid insertions in the protease have rarely been described in HIVinfected patients. One of these insertions has recently been described in codon 35, although its impact on resistance remains unknown. This study presents a case of an HIV variant with an insertion in codon 35 of the protease, described for the first time in Bauru, State of Sao Paulo, Brazil, circulating in a 38-year-old caucasian male with asymptomatic HIV infection since 1997. The variant isolated showed a codon 35 insertion of two amino acids in the protease: a threonine and an aspartic acid, resulting in the amino acid sequence E35E_TD.

A 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 confers protections against HIV-1 infection

2017 ◽  
Vol 19 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Mara Biasin ◽  
Manuela Sironi ◽  
Irma Saulle ◽  
Chiara Pontremoli ◽  
Micaela Garziano ◽  
...  
Keyword(s):  
Amino Acid ◽  
Deletion Polymorphism ◽  
Amino Acid Insertion ◽  
Hiv 1

scholarly journals A chimeric human APOBEC3A protein with a three amino acid insertion confers differential HIV-1 and adeno-associated virus restriction

Virology ◽  
2016 ◽  
Vol 498 ◽  
pp. 149-163 ◽  
Author(s):  
Yaqiong Wang ◽  
Zekun Wang ◽  
Ankita Pramanik ◽  
Mario L. Santiago ◽  
Jianming Qiu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Adeno Associated Virus ◽  
Amino Acid Insertion ◽  
Hiv 1
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