Highlights
- •Mutations in early HIV-1-infection collectively impair fitness of the T/F viruses.
- •Fitness loss is associated with reduced viral loads from viremia peak.
- •Testing mutations in the cognate T/F genome accurately determinates HIV-1 fitness.
Summary
Objective
Viral fitness plays an important role in HIV-1 evolution, transmission and pathogenesis.
However, how mutations accumulated during early infection affect viral fitness has
not been well studied.
Methods
Paired infectious molecular clones (IMCs) for transmitted/founder (T/F) and 6-month
(6-mo) viruses post infection were generated from 10 infected individuals to investigate
the impact of accumulated mutations on viral fitness by comparing 6-mo viruses to
their cognate T/F viruses.
Results
All ten 6-mo viruses were less fit than their cognate T/F viruses. Moreover, the fitness
losses of the 6-mo viruses correlated with the decrease in viral loads from the peak
of viremia.
Conclusion
These results show that the mutations accumulated during half a year post infection
collectively reduce viral fitness and thereby contribute to lowering viral loads.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of InfectionAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression.J Virol. 2000; 74 (PubMed PMID: 10982369. Pubmed Central PMCID: PMC102121): 9222-9233
- Changes in human immunodeficiency virus type 1 fitness and genetic diversity during disease progression.J Virol. 2005; 79 (PubMed PMID: 15994794. Pubmed Central PMCID: PMC1168764): 9006-9018
- The fitness cost of mutations associated with human immunodeficiency virus type 1 drug resistance is modulated by mutational interactions.J Virol. 2007; 81 (PubMed PMID: 17192300. Pubmed Central PMCID: PMC1865994): 3037-3041
- Transmission of HIV-1 CTL escape variants provides HLA-mismatched recipients with a survival advantage.PLoS Pathog. 2008; 4 (PubMed PMID: 18369479. Pubmed Central PMCID: PMC2265427)e1000033
- Transmission of HIV-1 GAG immune escape mutations is associated with reduced viral load in linked recipients.J Exp Med. 2008; 205 (PubMed PMID: 18426987. Pubmed Central PMCID: PMC2373834): 1009-1017
- Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703-positive individuals and their transmission recipients.J Exp Med. 2009; 206 (PubMed PMID: 19307327. Pubmed Central PMCID: PMC2715113): 909-921
- Fitness disadvantage of transitional intermediates contributes to dynamic change in the infecting-virus population during coreceptor switch in R5 simian/human immunodeficiency virus-infected macaques.J Virol. 2010; 84 (PubMed PMID: 20943985. Pubmed Central PMCID: PMC3004298): 12862-12871
- Replicative fitness of transmitted HIV-1 drives acute immune activation, proviral load in memory CD4+ t cells, and disease progression.Proc Natl Acad Sci U S A. 2015; 112 (Mar 24PubMed PMID: 25730868. Pubmed Central PMCID: PMC4378387): E1480-E1489
- The impact of HIV-1 within-host evolution on transmission dynamics.Curr Opin Virol. 2018; 28 (PubMed PMID: 29275182): 92-101
- Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.J Virol. 1994; 68 (PubMed PMID: 8207839. Pubmed Central PMCID: PMC236393): 4650-4655
- Antiviral pressure exerted by HIV-1-specific cytotoxic t lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus.Nat Med. 1997; 3 (PubMed PMID: 9018240): 205-211
- The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection.J Exp Med. 2009; 206 (PubMed PMID: 19487423. Pubmed Central PMCID: PMC2715063): 1253-1272
- Acute HIV-1 infection.N Engl J Med. 2011; 364 (PubMed PMID: 21591946. Pubmed Central PMCID: PMC3771113): 1943-1954
- Fitness cost of escape mutations in p24 gag in association with control of human immunodeficiency virus type 1.J Virol. 2006; 80 (PubMed PMID: 16537629. Pubmed Central PMCID: PMC1440414): 3617-3623
- HLA-B57/B*5801 human immunodeficiency virus type 1 elite controllers select for rare gag variants associated with reduced viral replication capacity and strong cytotoxic T-lymphocyte [corrected] recognition.J Virol. 2009; 83 (MarPubMed PMID: 19116253. Pubmed Central PMCID: PMC2648254): 2743-2755
- Variable fitness impact of HIV-1 escape mutations to cytotoxic t lymphocyte (CTL) response.PLoS Pathog. 2009; 5 (PubMed PMID: 19343217. Pubmed Central PMCID: PMC2659432)e1000365
- Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome.Retrovirology. 2012; 9 (PubMed PMID: 23110705. Pubmed Central PMCID: PMC3496648): 89
- Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation.Retrovirology. 2014; 11 (PubMed PMID: 25407514. Pubmed Central PMCID: PMC4264250): 101
- Role of CD8(+) T cells in the selection of HIV-1 immune escape mutations.Viral Immunol. 2017; 30 (Jan/FebPubMed PMID: 27805477): 3-12
- Escape and compensation from early HLA-B57-mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 GAG alter capsid interactions with cyclophilin A.J Virol. Nov 2007; 81 (PubMed PMID: 17728232. Pubmed Central PMCID: PMC2169025): 12608-12618
- Compensatory mutation partially restores fitness and delays reversion of escape mutation within the immunodominant HLA-B*5703-restricted GAG epitope in chronic human immunodeficiency virus type 1 infection.J Virol. Aug 2007; 81 (PubMed PMID: 17507468. Pubmed Central PMCID: PMC1951305): 8346-8351
- Escape from the dominant HLA-B27-restricted cytotoxic T-lymphocyte response in GAG is associated with a dramatic reduction in human immunodeficiency virus type 1 replication.J Virol. Nov 2007; 81 (Pubmed PMID: 17804494. Pubmed Central PMCID: PMC2169010): 12382-12393
- Reversion and T cell escape mutations compensate the fitness loss of a CD8+ T cell escape mutant in their cognate transmitted/founder virus.PLoS ONE. 2014; 9 (PubMed PMID: 25028937. Pubmed Central PMCID: PMC4100905)e102734
- Reduced viral replication capacity of human immunodeficiency virus type 1 subtype C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid protein.J Virol. 2009; 83 (MarPubMed PMID: 19109381. Pubmed Central PMCID: PMC2648284): 2460-2468
- Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies.Cell. 2014; 158 (PubMed PMID: 25065977. Pubmed Central PMCID: PMC4150607): 481-491
- Consequences of HLA-B*13-Associated escape mutations on HIV-1 replication and NEF function.J Virol. 2015; 89 (PubMed PMID: 26355081. Pubmed Central PMCID: PMC4645636): 11557-11571
- Accumulation of pol mutations selected by HLA-B*52:01-C*12:02 protective haplotype-restricted cytotoxic T lymphocytes causes low plasma viral load due to low viral fitness of mutant viruses.J Virol. 2017; 91 (PubMed PMID: 27903797. Pubmed Central PMCID: PMC5286884)
- Viral replication capacity as a correlate of hla B57/B5801-associated nonprogressive HIV-1 infection.J Immunol. 2007; 179 (PubMed PMID: 17709528): 3133-3143
- Human immunodeficiency virus type 1 fitness is a determining factor in viral rebound and set point in chronic infection.J Virol. 2003; 77 (PubMed PMID: 14645571. Pubmed Central PMCID: PMC296087): 13146-13155
- Assessing predicted HIV-1 replicative capacity in a clinical setting.PLoS Pathog. 2011; 7 (PubMed PMID: 22072960. Pubmed Central PMCID: PMC3207887)e1002321
- Virulence and pathogenesis of HIV-1 infection: an evolutionary perspective.Science. 2014; 343 (PubMed PMID: 24653038)1243727
- Relationship between in vitro human immunodeficiency virus type 1 replication rate and virus load in plasma.J Virol. 2003; 77 (PubMed PMID: 14581547. Pubmed Central PMCID: PMC253754): 12105-12112
- High viral fitness during acute HIV-1 infection.PLoS ONE. 2010; 5 (PubMed PMID: 20844589. Pubmed Central PMCID: PMC2936565)
- Influence of GAG-protease-mediated replication capacity on disease progression in individuals recently infected with HIV-1 subtype C.J Virol. 2011; 85 (Pubmed PMID: 21289112. Pubmed Central PMCID: PMC3126116): 3996-4006
- Role of transmitted GAG CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis.PLoS Pathog. 2012; 8 (PubMed PMID: 23209412. Pubmed Central PMCID: PMC3510241)e1003041
- In vitro replication kinetics of human immunodeficiency virus type 1 (HIV-1) variants in relation to virus load in long-term survivors of HIV-1 infection.J Infect Dis. 1998; 177 (MarPubMed PMID: 9498438): 600-610
- Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients.PLoS Pathog. 2015; 11 (PubMed PMID: 25569444. Pubmed Central PMCID: PMC4287535)e1004565
- Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.Proc Natl Acad Sci U S A. 2008; 105 (PubMed PMID: 18490657. Pubmed Central PMCID: PMC2387184): 7552-7557
- Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants.J Virol. 2009; 83 (PubMed PMID: 19193811. Pubmed Central PMCID: PMC2663249): 3556-3567
- Primary infection by a human immunodeficiency virus with atypical coreceptor tropism.J Virol. Oct 2011; 85 (PubMed PMID: 21835785. Pubmed Central PMCID: PMC3187499): 10669-10681
- Relative resistance of HIV-1 founder viruses to control by interferon-alpha.Retrovirology. 2013; 10 (PubMed PMID: 24299076. Pubmed Central PMCID: PMC3907080): 146
- Phenotypic properties of transmitted founder HIV-1.Proc Natl Acad Sci U S A. 2013; 110 (PubMed PMID: 23542380. Pubmed Central PMCID: PMC3637789): 6626-6633
- Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape.PLoS Pathog. 2012; 8 (PubMed PMID: 22693447. Pubmed Central PMCID: PMC3364956)e1002721
- Vertical T cell immunodominance and epitope entropy determine HIV-1 escape.J Clin Invest. 2013; 123 (PubMed PMID: 23221345. Pubmed Central PMCID: PMC3533301): 380-393
- Transmission of multiple HIV-1 subtype c transmitted/founder viruses into the same recipients was not determined by modest phenotypic differences.Sci Rep. 2016; 6 (PubMed PMID: 27909304. Pubmed Central PMCID: PMC5133561): 38130
- A strongly selected mutation in the HIV-1 genome is independent of T cell responses and neutralizing antibodies.Retrovirology. 2017; 14 (PubMed PMID: 29017536. Pubmed Central PMCID: PMC5634943): 46
- CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.Nucleic Acids Res. 1994; 22 (PubMed PMID: 7984417. Pubmed Central PMCID: PMC308517): 4673-4680
- Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection.J Exp Med. 2009; 206 (PubMed PMID: 19487424. Pubmed Central PMCID: PMC2715054): 1273-1289
- Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin alpha4beta7.PLoS Pathog. 2012; 8 (PubMed PMID: 22693444. Pubmed Central PMCID: PMC3364951)e1002686
- Detection of minor drug-resistant populations by parallel allele-specific sequencing.Nat Methods. 2007; 4 (PubMed PMID: 17206150): 123-125
- Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes.Science. 1999; 283 (PubMed PMID: 9933172): 857-860
- Central role of reverting mutations in HLA associations with human immunodeficiency virus set point.J Virol. 2008; 82 (PubMed PMID: 18596105. Pubmed Central PMCID: PMC2519667): 8548-8559
- Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection.J Virol. 2011; 85 (PubMed PMID: 21835793. Pubmed Central PMCID: PMC3187476): 10518-10528
- HLA-B*57 micropolymorphism shapes HLA allele-specific epitope immunogenicity, selection pressure, and HIV immune control.J Virol. 2012; 86 (PubMed PMID: 22090105. Pubmed Central PMCID: PMC3255844): 919-929
- Estimating relative fitness in viral competition experiments.J Virol. 2000; 74 (PubMed PMID: 11070001. Pubmed Central PMCID: PMC113186): 11067-11072
- Modeling and estimation of replication fitness of human immunodeficiency virus type 1 in vitro experiments by using a growth competition assay.J Virol. 2006; 80 (MarPubMed PMID: 16474144. Pubmed Central PMCID: PMC1395363): 2380-2389
- Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals.AIDS Res Ther. 2017; 14 (PubMed PMID: 28331526. Pubmed Central PMCID: PMC5359922): 15
Article info
Publication history
Published online: December 05, 2019
Accepted:
December 1,
2019
Identification
Copyright
© 2019 The British Infection Association. Published by Elsevier Ltd. All rights reserved.