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A second-site suppressor significantly improves the defective phenotype imposed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein.

ABSTRACT: The HIV-1 capsid (CA) protein plays an important role in virus assembly and infectivity. Previously, we showed that Ala substitutions in the N-terminal residues Trp23 and Phe40 cause a severely defective phenotype. In searching for mutations at these positions that result in a non-lethal phenotype, we identified one candidate, W23F. Mutant virions contained aberrant cores, but unlike W23A, also displayed some infectivity in a single-round replication assay and delayed replication kinetics in MT-4 cells. Following long-term passage in MT-4 cells, two second-site mutations were isolated. In particular, the W23F/V26I mutation partially restored the wild-type phenotype, including production of particles with conical cores and wild-type replication kinetics in MT-4 cells. A structural model is proposed to explain the suppressor phenotype. These findings describe a novel occurrence, namely suppression of a mutation in a hydrophobic residue that is critical for maintaining the structural integrity of CA and proper core assembly.

SUBMITTER: Tang S

PROVIDER: S-EPMC1851891 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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A second-site suppressor significantly improves the defective phenotype imposed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein.

Tang Shixing S Ablan Sherimay S Dueck Megan M Ayala-López Wilfredo W Soto Brenda B Caplan Margaret M Nagashima Kunio K Hewlett Indira K IK Freed Eric O EO Levin Judith G JG

Virology 20061019 1

The HIV-1 capsid (CA) protein plays an important role in virus assembly and infectivity. Previously, we showed that Ala substitutions in the N-terminal residues Trp23 and Phe40 cause a severely defective phenotype. In searching for mutations at these positions that result in a non-lethal phenotype, we identified one candidate, W23F. Mutant virions contained aberrant cores, but unlike W23A, also displayed some infectivity in a single-round replication assay and delayed replication kinetics in MT- ...[more]

PMID: 17055023

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Project description:There is a large literature showing that adult L2 learners, in contrast to children, often fail to acquire native-like competence in the second language. Because of such age effects, adult L2 learning is often viewed as "fundamentally different" from child acquisition and defective in some way. However, adult L2 learners do not always do worse than child learners. Several studies (e.g., Sasaki, 1997; Dąbrowska and Street, 2006; Street, 2017; Dąbrowska, 2019) found considerable overlap between L1 and L2 speakers' performance on tasks tapping morphosyntactic knowledge. Crucially, these studies used grammatical comprehension tasks (e.g., picture selection) to test mastery of "functional" grammar (i.e., grammatical contrasts which correspond to a clear difference in meaning, such as the assignment of agent and patient roles in sentences with noncanonical word order and quantifier scope). In contrast, most ultimate attainment studies (e.g., Johnson and Newport, 1989; Flege et al., 1999; DeKeyser, 2000; DeKeyser et al., 2010) used a grammaticality judgment task (GST) which assessed mastery of "decorative" grammar, i.e., grammatical morphemes such as tense and agreement markers which make relatively little contribution to the meaning conveyed by a sentence. In this study, we directly compared native speakers, late immersion learners, and classroom foreign language learners on tasks assessing both aspects of grammar. As in earlier studies, we found significant differences between native speakers and both non-native groups in performance on "decorative" grammar, particularly when performance was assessed using spoken rather than written stimuli. However, the differences in performance on the "functional" grammar task were much smaller and statistically non-significant. Furthermore, even in the "decorative" grammar task, there was more overlap between native speakers and late L2 learners than reported in earlier research. We argue that this is because earlier studies underestimated the amount of variation found in native speakers.

Dataset Information

A second-site suppressor significantly improves the defective phenotype imposed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein.

Publications

A second-site suppressor significantly improves the defective phenotype imposed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein.

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