Heterosexual transmission of human immunodeficiency virus type 1 subtype C in southern Brazil

Silveira, Jussara María; Santos, André F.; Martínez, Ana Maria Barral de; Goes, Livia R; Mendoza-Sassi, Raúl Andrés; Muniz, Cláudia P.; Tupinambás, Unaí; Soares, Marcelo A.; Greco, Dirceu Bartolomeu

doi:10.1016/j.jcv.2012.01.017

Cited by 22 publications

(28 citation statements)

References 37 publications

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“…[8][9][10][11][12][13][14][15][16] In the city of Rio Grande, one of the foci of this study, such an increase is clearly evident: from 22% in 2002 to 56% in 2010. 16,17 The introduction of highly active antiretroviral therapy (HAART) in HIV-infected patients is associated with a marked reduction in morbidity and mortality. 18,19 Resistance to antiretroviral (ARV) drugs is a major cause of treatment failure and has been associated with higher mortality rates.…”

Section: Introductionmentioning

confidence: 79%

“…Primers and PCR conditions for both reactions have been previously described. 14,16,28 Purified PCR products were sequenced with the Prism Ò BigDyeÔ Terminator Cycle Sequencing Ready Reaction Kit (Thermo Scientific, Carlsbad, USA) using the inner primers of each respective PCR reaction. DNA sequencing was carried out in an automated ABI 3130XL Genetic Analyzer (Thermo Scientific).…”

Section: Study Subjects and Sample Collectionmentioning

confidence: 99%

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Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil

Barral

Sousa

Santos

et al. 2017

AIDS Research and Human Retroviruses

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Mutations in the connection and RNase H C-terminal reverse transcriptase (RT) domains of HIV-1 have been shown to impact drug resistance to RT inhibitors. However, their impact in the context of non-B subtypes has been poorly assessed. This study aimed to characterize resistance-related mutations in the C-terminal portions of RT in treatment-failing patients from southern Brazil, a region with endemic HIV-1 subtype C (HIV-1C). Viral RNA was isolated and reverse transcribed from 280 infected subjects, and genomic regions were analyzed by polymerase chain reaction, DNA sequencing, and phylogenetic analysis. Two novel mutations, M357R and E529D, were evidenced in Brazilian HIV-1C strains from treatment-failing patients. In global viral isolates of subjects on treatment, M357R was selected in HIV-1C and CRF01_AE and E529D was selected in HIV-1 subtype B (HIV-1B). While most C-terminal RT mutations described for HIV-1B also occur in HIV-1C, this work pinpointed novel mutations that display subtype-specific predominance or occurrence.

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Section: Introductionmentioning

confidence: 79%

Section: Study Subjects and Sample Collectionmentioning

confidence: 99%

Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil

Barral

Sousa

Santos

et al. 2017

AIDS Research and Human Retroviruses

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“…In addition, in Guinea-Bissau, infection with recombinant A3/02 was associated with increased risk of AIDS or death compared with subtype A3 (14). There is also evidence for reduced subtype C Gag-protease function relative to subtype B, corresponding with slower disease progression in subtype C-infected individuals; in Brazil, where subtype C cocirculates with subtypes B and F1 and intersubtype recombinants, subtype C was associated with higher CD4 counts (18). However, there are conflicting reports of the disease progression rate of subtype C relative to that of subtypes A and D (12,(15)(16)(17)59).…”

Section: Discussionmentioning

confidence: 99%

“…There is also evidence that recombinant forms have a higher rate of progression to AIDS than does subtype A (10,14), although this was not observed in another study (12). There are conflicting reports regarding the rate of disease progression of subtype C relative to that of other subtypes (12,(15)(16)(17)(18). While there is general agreement that subtype C has a transmissibility rate at least equal to those of other M group subtypes (19,20), some studies have reported increased transmissibility of subtype C compared to subtypes A and D (21)(22)(23).…”

mentioning

confidence: 99%

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression

Kiguoya

Mann

Chopera

et al. 2017

J Virol

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There are marked differences in the spread and prevalence of HIV-1 subtypes worldwide, and differences in clinical progression have been reported. However, the biological reasons underlying these differences are unknown. Gag-protease is essential for HIV-1 replication, and Gag-protease-driven replication capacity has previously been correlated with disease progression. We show that Gag-protease replication capacity correlates significantly with that of whole isolates (r ϭ 0.51; P ϭ 0.04), indicating that Gag-protease is a significant contributor to viral replication capacity. Furthermore, we investigated subtype-specific differences in Gag-proteasedriven replication capacity using large well-characterized cohorts in Africa and the Americas. Patient-derived Gag-protease sequences were inserted into an HIV-1 NL4-3 backbone, and the replication capacities of the resulting recombinant viruses were measured in an HIV-1-inducible reporter T cell line by flow cytometry. Recombinant viruses expressing subtype C Gag-proteases exhibited substantially lower replication capacities than those expressing subtype B Gag-proteases (P Ͻ 0.0001); this observation remained consistent when representative Gag-protease sequences were engineered into an HIV-1 subtype C backbone. We identified Gag residues 483 and 484, located within the Alix-binding motif involved in virus budding, as major contributors to subtype-specific replicative differences. In East African cohorts, we observed a hierarchy of Gag-protease-driven replication capacities, i.e., subtypes A/C Ͻ D Ͻ intersubtype recombinants (P Ͻ 0.0029), which is consistent with reported intersubtype differences in disease progression. We thus hypothesize that the lower Gagprotease-driven replication capacity of subtypes A and C slows disease progression in individuals infected with these subtypes, which in turn leads to greater opportunity for transmission and thus increased prevalence of these subtypes.IMPORTANCE HIV-1 subtypes are unevenly distributed globally, and there are reported differences in their rates of disease progression and epidemic spread. The biological determinants underlying these differences have not been fully elucidated. Here, we show that HIV-1 Gag-protease-driven replication capacity correlates with Citation Kiguoya MW, Mann JK, Chopera D, Gounder K, Lee GQ, Hunt PW, Martin JN, Ball TB, Kimani J, Brumme ZL, Brockman MA, Ndung'u T. 2017. Subtype-specific differences in Gagprotease-driven replication capacity are consistent with intersubtype differences in HIV-1 disease progression. J Virol 91:e00253-17.

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“…Whereas in POA, the association between men having sex with men (MSM) and HIV-1B disappeared in more recent sampling because of an expansion of HIV-1C in heterosexual (HET) and MSM groups (45), compartmentalized epidemics are still observed in other cities in the southern region, including Paraná, which could be explained by later introduction of HIV-1C (4,(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Contribution of Epidemiological Predictors in Unraveling the Phylogeographic History of HIV-1 Subtype C in Brazil

Gräf

Vrancken

Junqueira

et al. 2015

J Virol

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Heterosexual transmission of human immunodeficiency virus type 1 subtype C in southern Brazil

Abstract: The molecular epidemiology of HIV-1 in the southernmost Brazil is currently steady with predominance of HIV-1C. This is the first study showing a robust association of the infection by this subtype and heterosexual transmission in the state of Rio Grande do Sul, Brazil.

Cited by 22 publications

References 37 publications

Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil

Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression

Contribution of Epidemiological Predictors in Unraveling the Phylogeographic History of HIV-1 Subtype C in Brazil

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