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Author |
Sanjuan, R.; Nebot, M.; Peris, J.B.; Alcami, J. |
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Title |
Immune Activation Promotes Evolutionary Conservation of T-Cell Epitopes in HIV-1 |
Type |
Journal Article |
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Year |
2013 |
Publication |
Plos Biology |
Abbreviated Journal |
PLoS. Biol. |
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Volume |
11 |
Issue |
4 |
Pages |
e1001523 - 10pp |
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Keywords |
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Abstract |
The immune system should constitute a strong selective pressure promoting viral genetic diversity and evolution. However, HIV shows lower sequence variability at T-cell epitopes than elsewhere in the genome, in contrast with other human RNA viruses. Here, we propose that epitope conservation is a consequence of the particular interactions established between HIV and the immune system. On one hand, epitope recognition triggers an anti-HIV response mediated by cytotoxic T-lymphocytes (CTLs), but on the other hand, activation of CD4(+) helper T lymphocytes (T-H cells) promotes HIV replication. Mathematical modeling of these opposite selective forces revealed that selection at the intrapatient level can promote either T-cell epitope conservation or escape. We predict greater conservation for epitopes contributing significantly to total immune activation levels (immunodominance), and when T-H cell infection is concomitant to epitope recognition (transinfection). We suggest that HIV-driven immune activation in the lymph nodes during the chronic stage of the disease may offer a favorable scenario for epitope conservation. Our results also support the view that some pathogens draw benefits from the immune response and suggest that vaccination strategies based on conserved T-H epitopes may be counterproductive. |
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Address |
Univ Valencia, Inst Cavanilles Biodiversitat & Biol Evolut, Valencia, Spain, Email: rafael.sanjuan@uv.es |
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Publisher |
Public Library Science |
Place of Publication |
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Language |
English |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
1545-7885 |
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Conference |
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Notes |
WOS:000318687800003 |
Approved |
no |
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Is ISI |
yes |
International Collaboration |
no |
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Call Number |
IFIC @ pastor @ |
Serial |
1446 |
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Permanent link to this record |
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Author |
Sanjuan, R.; Nebot, M.; Chirico, N.; Mansky, L.M.; Belshaw, R. |
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Title |
Viral Mutation Rates |
Type |
Journal Article |
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Year |
2010 |
Publication |
Journal of Virology |
Abbreviated Journal |
J. Virol. |
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Volume |
84 |
Issue |
19 |
Pages |
9733-9748 |
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Keywords |
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Abstract |
Accurate estimates of virus mutation rates are important to understand the evolution of the viruses and to combat them. However, methods of estimation are varied and often complex. Here, we critically review over 40 original studies and establish criteria to facilitate comparative analyses. The mutation rates of 23 viruses are presented as substitutions per nucleotide per cell infection (s/n/c) and corrected for selection bias where necessary, using a new statistical method. The resulting rates range from 10(-8) to 10(-6) s/n/c for DNA viruses and from 10(-6) to 10(-4) s/n/c for RNA viruses. Similar to what has been shown previously for DNA viruses, there appears to be a negative correlation between mutation rate and genome size among RNA viruses, but this result requires further experimental testing. Contrary to some suggestions, the mutation rate of retroviruses is not lower than that of other RNA viruses. We also show that nucleotide substitutions are on average four times more common than insertions/deletions (indels). Finally, we provide estimates of the mutation rate per nucleotide per strand copying, which tends to be lower than that per cell infection because some viruses undergo several rounds of copying per cell, particularly double-stranded DNA viruses. A regularly updated virus mutation rate data set will be available at www.uv.es/rsanjuan/virmut. |
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Address |
[Sanjuan, Rafael] Univ Valencia, Inst Cavanilles Biodiversitat & Biol Evolutiva, Dept Genet, Valencia 46980, Spain, Email: rafael.sanjuan@uv.es |
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Publisher |
Amer Soc Microbiology |
Place of Publication |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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ISSN |
0022-538x |
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Conference |
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Notes |
ISI:000282641800008 |
Approved |
no |
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Is ISI |
yes |
International Collaboration |
yes |
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Call Number |
IFIC @ elepoucu @ |
Serial |
371 |
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Author |
Peris, J.B.; Davis, P.; Cuevas, J.M.; Nebot, M.; Sanjuan, R. |
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Title |
Distribution of Fitness Effects Caused by Single-Nucleotide Substitutions in Bacteriophage f1 |
Type |
Journal Article |
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Year |
2010 |
Publication |
Genetics |
Abbreviated Journal |
Genetics |
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Volume |
185 |
Issue |
2 |
Pages |
603-U308 |
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Keywords |
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Abstract |
Empirical knowledge of the fitness effects of mutations is important for understanding many evolutionary processes, yet this knowledge is often hampered by several sources of measurement error and bias. Most of these problems can be solved using site-directed mutagenesis to engineer single mutations, an approach particularly suited for viruses due to their small genomes. Here, we used this technique to measure the fitness effect of 100 single-nucleotide substitutions in the bacteriophage f1, a filamentous single-strand DNA virus. We found that approximately one-fifth of all mutations are lethal. Viable ones reduced fitness by 11% on average and were accurately described by a log-normal distribution. More than 90% of synonymous substitutions were selectively neutral, while those affecting intergenic regions reduced fitness by 14% on average. Mutations leading to amino acid substitutions had an overall mean deleterious effect of 37%, which increased to 45% for those changing the amino acid polarity. Interestingly, mutations affecting early steps of the infection cycle tended to be more deleterious than those affecting late steps. Finally, we observed at least two beneficial mutations. Our results confirm that high mutational sensitivity is a general property of viruses with small genomes, including RNA and single-strand DNA viruses infecting animals, plants, and bacteria. |
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Address |
[Peris, Joan B.; Davis, Paulina; Cuevas, Jose M.; Sanjuan, Rafael] Univ Valencia, Inst Cavanilles Biodiversitat & Biol Evolut, Valencia 46980, Spain, Email: rafael.sanjuan@uv.es |
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Corporate Author |
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Thesis |
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Publisher |
Genetics Soc Am |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
0016-6731 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
ISI:000281905200017 |
Approved |
no |
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Is ISI |
yes |
International Collaboration |
no |
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Call Number |
IFIC @ elepoucu @ |
Serial |
383 |
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Permanent link to this record |
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Author |
Nebot, M.; Botella, F.J.; Branco, G.C. |
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Title |
Vacuum induced CP violation generating a complex CKM matrix with controlled scalar FCNC |
Type |
Journal Article |
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Year |
2019 |
Publication |
European Physical Journal C |
Abbreviated Journal |
Eur. Phys. J. C |
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Volume |
79 |
Issue |
8 |
Pages |
711 - 23pp |
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Keywords |
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Abstract |
We propose. a viable minimal model with spontaneous CP violation in the framework of a two Higgs doublet model. The model is based on a generalised Branco-Grimus-Lavoura model with a flavoured Z(2) symmetry, under which two of the quark families are even and the third one is odd. The lagrangian respects CP invariance, but the vacuum has a CP violating phase, which is able to generate a complex CKM matrix, with the rephasing invariant strength of CP violation compatible with experiment. The question of scalar mediated flavour changing neutral couplings is carefully studied. In particular we point out a deep connection between the generation of a complex CKM matrix from a vacuum phase and the appearance of scalar FCNC. The scalar sector is presented in detail, showing that the new scalars are necessarily lighter than 1 TeV. A complete analysis of the model including the most relevant constraints is performed, showing that it is viable and that it has definite implications for the observation of New Physics signals in, for example, flavour changing Higgs decays or the discovery of the new scalars at the LHC. We give special emphasis to processes like t -> hc, hu, as well as h -> bs, bd, which are relevant for the LHC and the ILC. |
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Address |
[Nebot, Miguel; Branco, Gustavo C.] UL, Dept Fis, Inst Super Tecn, Av Rovisco Pais 1, P-1049001 Lisbon, Portugal, Email: miguel.r.nebot.gomez@tecnico.ulisboa.pt; |
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Corporate Author |
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Thesis |
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Publisher |
Springer |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
1434-6044 |
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Conference |
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Notes |
WOS:000483225300003 |
Approved |
no |
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Is ISI |
yes |
International Collaboration |
yes |
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Call Number |
IFIC @ pastor @ |
Serial |
4130 |
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Permanent link to this record |
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Author |
Nebot, M. |
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Title |
Bounded masses in two Higgs doublets models, spontaneous CP violation and Z(2) symmetry |
Type |
Journal Article |
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Year |
2020 |
Publication |
Physical Review D |
Abbreviated Journal |
Phys. Rev. D |
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Volume |
102 |
Issue |
11 |
Pages |
115002 - 16pp |
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Keywords |
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Abstract |
In two Higgs doublet models (2HDMs) shaped by some unbroken symmetry, imposing perturbativity requirements on the quartic couplings can imply that the allowed masses of all the fundamental scalars are bounded from above. This important property is analyzed in detail for the only two realistic 2HDMs with an exact symmetry, the case with Z(2) symmetry and the case with CP symmetry. It is also noticeable that one exception arises in each case: when the vacuum is assumed to respect the imposed symmetry, a decoupling regime can nevertheless appear without violating perturbativity requirements. In both models with an exact symmetry and no decoupling regime, soft symmetry breaking terms can however lead to a decoupling regime: the possibility that this regime might be unnatural, since it requires some fine-tuning, is also analyzed. |
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Address |
[Nebot, Miguel] Univ Lisboa UL, Inst Super Tecn IST, Ctr Fis Teor Particulas CFTP, P-1049001 Lisbon, Portugal, Email: Miguel.Nebot@uv.es |
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Corporate Author |
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Thesis |
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Publisher |
Amer Physical Soc |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
2470-0010 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
WOS:000594994400009 |
Approved |
no |
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Is ISI |
yes |
International Collaboration |
yes |
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Call Number |
IFIC @ pastor @ |
Serial |
4628 |
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Permanent link to this record |