scholarly journals Functional conservation and coherence of HIV-1 subtype A Vpu alleles

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Bizhan Romani ◽  
Amirarsalan Kavyanifard ◽  
Elham Allahbakhshi

Abstract Functional studies of HIV-1 proteins are normally conducted using lab adapted strains of HIV-1. The extent of those functions in clinical strains is sometimes unknown. In this study, we amplified and sequenced HIV-1 Vpu from 10 Iranian patients infected with HIV-1. Phylogenetic analysis indicated that the Vpu alleles were closely related to the CRF35_AD from Iran and subtype A Vpu. We addressed some of the well-established functions of the HIV-1 Vpu, as well as some of its recently reported functions. Ability of the clinical strains of subtype A Vpu alleles for downregulation of CD4 was similar to that of the lab adapted NL4.3 Vpu. Majority of the subtype A Vpu alleles performed stronger than NL4.3 Vpu for downregulation of SNAT1. The Vpu alleles differentially induced downregulation of HLA-C, ranging from no effect to 88% downregulation of surface HLA-C. Downregulation of tetherin and enhancement of virus release was similar for the subtype A Vpu alleles and NL4.3. Subtype A Vpu alleles were more potent when compared with NL4.3 for inhibition of NF-κB activation. Our study shows that subtype A Vpu alleles exert the classical functions of HIV-1 Vpu.

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Bizhan Romani ◽  
Amirarsalan Kavyanifard ◽  
Elham Allahbakhshi

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Bizhan Romani ◽  
Amirarsalan Kavyanifard ◽  
Elham Allahbakhshi

2021 ◽  
Author(s):  
Ana Carolina de Oliveira Luz ◽  
Wilson José da Silva Junior ◽  
José Bandeira do Nascimento Junior ◽  
Julia Mariana Assis da Silva ◽  
Valdir de Queiroz Balbino ◽  
...  

Author(s):  
Sundararajan Venkatesan ◽  
Steven M. Holland ◽  
Nafees Ahmad ◽  
Paul Wingfield ◽  
Ratan K. Maitra ◽  
...  
Keyword(s):  

2010 ◽  
Vol 11 (3) ◽  
pp. 243
Author(s):  
Saber Jelokhani-Niaraki ◽  
Majid Esmaelizad ◽  
Morteza Daliri ◽  
Rasoul Vaez-Torshizi ◽  
Morteza Kamalzadeh ◽  
...  

Virology ◽  
2006 ◽  
Vol 345 (2) ◽  
pp. 328-336 ◽  
Author(s):  
Milka A. Rodriguez ◽  
Yue Chen ◽  
Jodi K. Craigo ◽  
Ramdas Chatterjee ◽  
Deena Ratner ◽  
...  

2009 ◽  
Vol 83 (11) ◽  
pp. 5592-5605 ◽  
Author(s):  
Awet Abraha ◽  
Immaculate L. Nankya ◽  
Richard Gibson ◽  
Korey Demers ◽  
Denis M. Tebit ◽  
...  

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) subtype C is the dominant subtype globally, due largely to the incidence of subtype C infections in sub-Saharan Africa and east Asia. We compared the relative replicative fitness (ex vivo) of the major (M) group of HIV-1 subtypes A, B, C, D, and CRF01_AE and group O isolates. To estimate pathogenic fitness, pairwise competitions were performed between CCR5-tropic (R5) or CXCR4-tropic (X4) virus isolates in peripheral blood mononuclear cells (PBMC). A general fitness order was observed among 33 HIV-1 isolates; subtype B and D HIV-1 isolates were slightly more fit than the subtype A and dramatically more fit than the 12 subtype C isolates. All group M isolates were more fit (ex vivo) than the group O isolates. To estimate ex vivo transmission fitness, a subset of primary HIV-1 isolates were examined in primary human explants from penile, cervical, and rectal tissues. Only R5 isolates and no X4 HIV-1 isolates could replicate in these tissues, whereas the spread to PM1 cells was dependent on active replication and passive virus transfer. In tissue competition experiments, subtype C isolates could compete with and, in some cases, even win over subtype A and D isolates. However, when the migratory cells from infected tissues were mixed with a susceptible cell line, the subtype C isolates were outcompeted by other subtypes, as observed in experiments with PBMC. These findings suggest that subtype C HIV-1 isolates might have equal transmission fitness but reduced pathogenic fitness relative to other group M HIV-1 isolates.


1999 ◽  
Vol 37 (1) ◽  
pp. 110-116 ◽  
Author(s):  
K. Triques ◽  
J. Coste ◽  
J. L. Perret ◽  
C. Segarra ◽  
E. Mpoudi ◽  
...  

Three versions of a commercial human immunodeficiency virus (HIV) type 1 (HIV-1) load test (the AMPLICOR HIV-1 MONITOR Test versions 1.0, 1.0+, and 1.5; Roche Diagnostics, Branchburg, N.J.) were evaluated for their ability to detect and quantify HIV-1 RNA of different genetic subtypes. Plasma samples from 96 patients infected with various subtypes of HIV-1 (55 patients infected with subtype A, 9 with subtype B, 21 with subtype C, 2 with subtype D, 7 with subtype E, and 2 with subtype G) and cultured virus from 29 HIV-1 reference strains (3 of subtype A, 6 of subtype B, 5 of subtype C, 3 of subtype D, 8 of subtype E, 3 of subtype F, and 1 of subtype G) were tested. Detection of subtypes A and E was significantly improved with versions 1.0+ and 1.5 compared to that with version 1.0, whereas detection of subtypes B, C, D, and G was equivalent with the three versions. Versions 1.0, 1.0+, and 1.5 detected 65, 98, and 100% of the subtype A-infected samples from patients, respectively, and 71, 100, and 100% of the subtype E-infected samples from patients, respectively. Version 1.5 yielded a significant increase in viral load for samples infected with subtypes A and E (greater than 1 log10 HIV RNA copies/ml). For samples infected with subtype B, C, and D and tested with version 1.5, only a slight increase in viral load was observed (<0.5 log10). We also evaluated a prototype automated version of the test that uses the same PCR primers as version 1.5. The results with the prototype automated test were highly correlated with those of the version 1.5 test for all subtypes, but were lower overall. The AMPLICOR HIV-1 MONITOR Test, version 1.5, yielded accurate measurement of the HIV load for all HIV-1 subtypes tested, which should allow the test to be used to assess disease prognosis and response to antiretroviral treatment in patients infected with a group M HIV-1 subtype.


2015 ◽  
Vol 33 ◽  
pp. 197-205 ◽  
Author(s):  
Francisco Díez-Fuertes ◽  
Marina Cabello ◽  
Michael M. Thomson
Keyword(s):  

Author(s):  
Emmanuel Ndashimye ◽  
Yue Li ◽  
Paul S Reyes ◽  
Mariano Avino ◽  
Abayomi S Olabode ◽  
...  

Abstract Objectives The second-generation integrase strand transfer inhibitor (INSTI) bictegravir is becoming accessible in low- and middle-income countries (LMICs), and another INSTI, cabotegravir, has recently been approved as a long-acting injectable. Data on bictegravir and cabotegravir susceptibility in raltegravir-experienced HIV-1 subtype A- and D-infected patients carrying drug resistance mutations (DRMs) remain very scarce in LMICs. Patients and methods HIV-1 integrase (IN)-recombinant viruses from eight patients failing raltegravir-based third-line therapy in Uganda were genotypically and phenotypically tested for susceptibility to bictegravir and cabotegravir. Ability of these viruses to integrate into human genomes was assessed in MT-4 cells. Results HIV-1 IN-recombinant viruses harbouring single primary mutations (N155H or Y143R/S) or in combination with secondary INSTI mutations (T97A, M50I, L74IM, E157Q, G163R or V151I) were susceptible to both bictegravir and cabotegravir. However, combinations of primary INSTI-resistance mutations such as E138A/G140A/G163R/Q148R or E138K/G140A/S147G/Q148K led to decreased susceptibility to both cabotegravir (fold change in EC50 values from 429 to 1000×) and bictegravir (60 to 100×), exhibiting a high degree of cross-resistance. However, these same IN-recombinant viruses showed impaired integration capacity (14% to 48%) relative to the WT HIV-1 NL4-3 strain in the absence of drug. Conclusions Though not currently widely accessible in most LMICs, bictegravir and cabotegravir offer a valid alternative to HIV-infected individuals harbouring subtype A and D HIV-1 variants with reduced susceptibility to first-generation INSTIs but previous exposure to raltegravir may reduce efficacy, more so with cabotegravir.


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