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

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.

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Erratum: Functional conservation and coherence of HIV-1 subtype A Vpu alleles

Scientific Reports ◽

10.1038/srep46882 ◽

2017 ◽

Vol 7 (1) ◽

Author(s):

Bizhan Romani ◽

Amirarsalan Kavyanifard ◽

Elham Allahbakhshi

Keyword(s):

Functional Conservation ◽

Subtype A ◽

Hiv 1

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Construction and characterization of an infectious molecular clone of HIV-1 subtype A of Indian origin

Virology ◽

10.1016/j.virol.2005.09.053 ◽

2006 ◽

Vol 345 (2) ◽

pp. 328-336 ◽

Cited By ~ 14

Author(s):

Milka A. Rodriguez ◽

Yue Chen ◽

Jodi K. Craigo ◽

Ramdas Chatterjee ◽

Deena Ratner ◽

...

Keyword(s):

Infectious Molecular Clone ◽

Molecular Clone ◽

Indian Origin ◽

Subtype A ◽

Hiv 1

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CCR5- and CXCR4-Tropic Subtype C Human Immunodeficiency Virus Type 1 Isolates Have a Lower Level of Pathogenic Fitness than Other Dominant Group M Subtypes: Implications for the Epidemic

Journal of Virology ◽

10.1128/jvi.02051-08 ◽

2009 ◽

Vol 83 (11) ◽

pp. 5592-5605 ◽

Cited By ~ 63

Author(s):

Awet Abraha ◽

Immaculate L. Nankya ◽

Richard Gibson ◽

Korey Demers ◽

Denis M. Tebit ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Ex Vivo ◽

Sub Saharan Africa ◽

Subtype C ◽

Immunodeficiency Virus ◽

Subtype A ◽

Hiv 1

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.

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Efficiencies of Four Versions of the AMPLICOR HIV-1 MONITOR Test for Quantification of Different Subtypes of Human Immunodeficiency Virus Type 1

Journal of Clinical Microbiology ◽

10.1128/jcm.37.1.110-116.1999 ◽

1999 ◽

Vol 37 (1) ◽

pp. 110-116 ◽

Cited By ~ 74

Author(s):

K. Triques ◽

J. Coste ◽

J. L. Perret ◽

C. Segarra ◽

E. Mpoudi ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Load ◽

Pcr Primers ◽

Load Test ◽

Subtype C ◽

Subtype B ◽

Immunodeficiency Virus ◽

Subtype A ◽

Hiv 1

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.

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Bayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union’s countries

Infection Genetics and Evolution ◽

10.1016/j.meegid.2015.05.003 ◽

2015 ◽

Vol 33 ◽

pp. 197-205 ◽

Cited By ~ 23

Author(s):

Francisco Díez-Fuertes ◽

Marina Cabello ◽

Michael M. Thomson

Keyword(s):

Subtype A ◽

Hiv 1

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High-level resistance to bictegravir and cabotegravir in subtype A- and D-infected HIV-1 patients failing raltegravir with multiple resistance mutations

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkab276 ◽

2021 ◽

Author(s):

Emmanuel Ndashimye ◽

Yue Li ◽

Paul S Reyes ◽

Mariano Avino ◽

Abayomi S Olabode ◽

...

Keyword(s):

Cross Resistance ◽

Strand Transfer ◽

Resistance Mutations ◽

Middle Income ◽

Recombinant Viruses ◽

Third Line ◽

Long Acting ◽

High Level ◽

Subtype A ◽

Hiv 1

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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Reconstruction of the Genetic History and the Current Spread of HIV-1 Subtype A in Germany

Journal of Virology ◽

10.1128/jvi.02238-18 ◽

2019 ◽

Vol 93 (12) ◽

Author(s):

Kirsten Hanke ◽

Nuno Rodrigues Faria ◽

Denise Kühnert ◽

Kaveh Pouran Yousef ◽

Andrea Hauser ◽

...

Keyword(s):

Public Health ◽

Eastern Africa ◽

Heterosexual Transmission ◽

Western European Country ◽

Eastern European ◽

African Lineage ◽

Current Spread ◽

Subtype A ◽

The Impact ◽

Hiv 1

ABSTRACT HIV-1 non-B infections have been increasing in Europe for several years. In Germany, subtype A belongs to the most abundant non-B subtypes showing an increasing prevalence of 8.3% among new infections in 2016. Here we trace the origin and examine the current spread of the German HIV-1 subtype A epidemic. Bayesian coalescence and birth-death analyses were performed with 180 German HIV-1 pol sequences and 528 related and publicly available sequences to reconstruct the population dynamics and fluctuations for each of the transmission groups. Our reconstructions indicate two distinct sources of the German subtype A epidemic, with an Eastern European and an Eastern African lineage both cocirculating in the country. A total of 13 German-origin clusters were identified; among these, 6 clusters showed recent activity. Introductions leading to further countrywide spread originated predominantly from Eastern Africa when introduced before 2005. Since 2005, however, spreading introductions have occurred exclusively within the Eastern European clade. Moreover, we observed changes in the main route of subtype A transmission. The beginning of the German epidemic (1985 to 1995) was dominated by heterosexual transmission of the Eastern African lineage. Since 2005, transmissions among German men who have sex with men (MSM) have been increasing and have been associated with the Eastern European lineage. Infections among people who inject drugs dominated between 1998 and 2005. Our findings on HIV-1 subtype A infections provide new insights into the spread of this virus and extend the understanding of the HIV epidemic in Germany. IMPORTANCE HIV-1 subtype A is the second most prevalent subtype worldwide, with a high prevalence in Eastern Africa and Eastern Europe. However, an increase of non-B infections, including subtype A infections, has been observed in Germany and other European countries. There has simultaneously been an increased flow of refugees into Europe and especially into Germany, raising the question of whether the surge in non-B infections resulted from this increased immigration or whether German transmission chains are mainly involved. This study is the first comprehensive subtype A study from a western European country analyzing in detail its phylogenetic origin, the impact of various transmission routes, and its current spread. The results and conclusions presented provide new and substantial insights for virologists, epidemiologists, and the general public health sector. In this regard, they should be useful to those authorities responsible for developing public health intervention strategies to combat the further spread of HIV/AIDS.

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