2017
DOI: 10.1101/235630
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Mapping mutational effects along the evolutionary landscape of HIV envelope

Hugh K. Haddox
1
,
Adam S. Dingens
2
,
Sarah K. Hilton
3
et al.

Abstract: The immediate evolutionary space accessible to HIV is largely determined by how single amino-acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here we quantify the effects on viral growth of all amino-acid mutations to two HIV envelope (Env) proteins that differ at >100 residues. Most mutations similarly affect both Envs, but the amino-acid preferences of a minority of sites have clearly shifted.… Show more

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Cited by 25 publications

(74 citation statements)
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“…Similar to previous DMS experiments, the frequency of stop codons in post-selected samples was reduced to 19-24% of their frequency in the mutant plasmid library (Figure 2b), evidence that our DMS strategy effectively selected for functional Env variants (17, 20). Frequencies of nonsynonymous mutations were also depleted in post-selected samples compared to pre-selected plasmid libraries, consistent with previous reports that amino acid substitutions in Env are generally deleterious (Figure 2b) (14, 15).…”
Section: Resultssupporting
confidence: 90%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…Similar to previous DMS experiments, the frequency of stop codons in post-selected samples was reduced to 19-24% of their frequency in the mutant plasmid library (Figure 2b), evidence that our DMS strategy effectively selected for functional Env variants (17, 20). Frequencies of nonsynonymous mutations were also depleted in post-selected samples compared to pre-selected plasmid libraries, consistent with previous reports that amino acid substitutions in Env are generally deleterious (Figure 2b) (14, 15).…”
Section: Resultssupporting
confidence: 90%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…S5B and C). DMS experiments were performed in duplicate, which produced similar results (R 2 = ~0.5) as in the case of previous studies conducted on HIV and influenza pathology with library viruses (20,21) (Fig. S6A).…”
Section: No Complete Escape Mutation In Deep Mutational Scanning Of T...supporting
confidence: 60%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…These shifts between H3 and H1 are much larger than expected from the null distribution that would be observed purely from experimental noise. They are also much larger than the shifts previously observed between two HIV Envs with 86% aminoacid identity (27). However, the typical shift between H3 and H1 is still smaller than that observed when comparing HA to the non-homologous HIV Env protein.…”
Section: Our Measurements Can Help Distinguish Between Mutationscontrasting
confidence: 57%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
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