FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2106872247> ?p ?o ?g. }

• W2106872247 endingPage "7752" @default.
• W2106872247 startingPage "7738" @default.
• W2106872247 abstract "ABSTRACT Myxovirus resistance 2 (Mx2/MxB) has recently been uncovered as an effector of the anti-HIV-1 activity of type I interferons (IFNs) that inhibits HIV-1 at an early stage postinfection, after reverse transcription but prior to proviral integration into host DNA. The mechanistic details of Mx2 antiviral activity are not yet understood, but a few substitutions in the HIV-1 capsid have been shown to confer resistance to Mx2. Through a combination of in vitro evolution and unbiased mutagenesis, we further map the determinants of sensitivity to Mx2 and reveal that multiple capsid (CA) surfaces define sensitivity to Mx2. Intriguingly, we reveal an unanticipated sensitivity determinant within the C-terminal domain of capsid. We also report that Mx2s derived from multiple primate species share the capacity to potently inhibit HIV-1, whereas selected nonprimate orthologs have no such activity. Like TRIM5α, another CA targeting antiretroviral protein, primate Mx2s exhibit species-dependent variation in antiviral specificity against at least one extant virus and multiple HIV-1 capsid mutants. Using a combination of chimeric Mx2 proteins and evolution-guided approaches, we reveal that a single residue close to the N terminus that has evolved under positive selection can determine antiviral specificity. Thus, the variable N-terminal region can define the spectrum of viruses inhibited by Mx2. IMPORTANCE Type I interferons (IFNs) inhibit the replication of most mammalian viruses. IFN stimulation upregulates hundreds of different IFN-stimulated genes (ISGs), but it is often unclear which ISGs are responsible for inhibition of a given virus. Recently, Mx2 was identified as an ISG that contributes to the inhibition of HIV-1 replication by type I IFN. Thus, Mx2 might inhibit HIV-1 replication in patients, and this inhibitory action might have therapeutic potential. The mechanistic details of how Mx2 inhibits HIV-1 are currently unclear, but the HIV-1 capsid protein is the likely viral target. Here, we determine the regions of capsid that specify sensitivity to Mx2. We demonstrate that Mx2 from multiple primates can inhibit HIV-1, whereas Mx2 from other mammals (dogs and sheep) cannot. We also show that primate variants of Mx2 differ in the spectrum of lentiviruses they inhibit and that a single residue in Mx2 can determine this antiviral specificity." @default.
• W2106872247 created "2016-06-24" @default.
• W2106872247 creator A5000480501 @default.
• W2106872247 creator A5015229811 @default.
• W2106872247 creator A5016904260 @default.
• W2106872247 creator A5018160359 @default.
• W2106872247 creator A5027557443 @default.
• W2106872247 creator A5053636210 @default.
• W2106872247 creator A5057137507 @default.
• W2106872247 creator A5061038601 @default.
• W2106872247 creator A5061062606 @default.
• W2106872247 creator A5065830204 @default.
• W2106872247 creator A5082442388 @default.
• W2106872247 creator A5085223765 @default.
• W2106872247 date "2014-07-15" @default.
• W2106872247 modified "2023-10-13" @default.
• W2106872247 title "Host and Viral Determinants of Mx2 Antiretroviral Activity" @default.
• W2106872247 cites W1503306485 @default.
• W2106872247 cites W1964324053 @default.
• W2106872247 cites W1964567249 @default.
• W2106872247 cites W1968918264 @default.
• W2106872247 cites W1970678134 @default.
• W2106872247 cites W1974784632 @default.
• W2106872247 cites W1977487387 @default.
• W2106872247 cites W1978743770 @default.
• W2106872247 cites W1985849199 @default.
• W2106872247 cites W1986829091 @default.
• W2106872247 cites W1987170068 @default.
• W2106872247 cites W1992727018 @default.
• W2106872247 cites W1996798386 @default.
• W2106872247 cites W1998938204 @default.
• W2106872247 cites W2001375348 @default.
• W2106872247 cites W2003527687 @default.
• W2106872247 cites W2004322145 @default.
• W2106872247 cites W2007089157 @default.
• W2106872247 cites W2007091097 @default.
• W2106872247 cites W2010458160 @default.
• W2106872247 cites W2019019911 @default.
• W2106872247 cites W2019039109 @default.
• W2106872247 cites W2021064626 @default.
• W2106872247 cites W2021885135 @default.
• W2106872247 cites W2027680432 @default.
• W2106872247 cites W2030277568 @default.
• W2106872247 cites W2033378491 @default.
• W2106872247 cites W2035166969 @default.
• W2106872247 cites W2043726848 @default.
• W2106872247 cites W2046183549 @default.
• W2106872247 cites W2050400345 @default.
• W2106872247 cites W2059722830 @default.
• W2106872247 cites W2060448494 @default.
• W2106872247 cites W2069554621 @default.
• W2106872247 cites W2072769067 @default.
• W2106872247 cites W2074937939 @default.
• W2106872247 cites W2075426476 @default.
• W2106872247 cites W2077176254 @default.
• W2106872247 cites W2077915242 @default.
• W2106872247 cites W2078646756 @default.
• W2106872247 cites W2079671323 @default.
• W2106872247 cites W2083512827 @default.
• W2106872247 cites W2084131702 @default.
• W2106872247 cites W2085704334 @default.
• W2106872247 cites W2088005137 @default.
• W2106872247 cites W2089329920 @default.
• W2106872247 cites W2100892474 @default.
• W2106872247 cites W2103162105 @default.
• W2106872247 cites W2103182811 @default.
• W2106872247 cites W2103546861 @default.
• W2106872247 cites W2108823152 @default.
• W2106872247 cites W2109130469 @default.
• W2106872247 cites W2111673257 @default.
• W2106872247 cites W2112507995 @default.
• W2106872247 cites W2113371722 @default.
• W2106872247 cites W2116713053 @default.
• W2106872247 cites W2117091532 @default.
• W2106872247 cites W2119104567 @default.
• W2106872247 cites W2119609500 @default.
• W2106872247 cites W2120902492 @default.
• W2106872247 cites W2122523609 @default.
• W2106872247 cites W2124493183 @default.
• W2106872247 cites W2126189632 @default.
• W2106872247 cites W2126728919 @default.
• W2106872247 cites W2127322768 @default.
• W2106872247 cites W2134559961 @default.
• W2106872247 cites W2138302939 @default.
• W2106872247 cites W2138468602 @default.
• W2106872247 cites W2140028978 @default.
• W2106872247 cites W2142533264 @default.
• W2106872247 cites W2143015604 @default.
• W2106872247 cites W2148372587 @default.
• W2106872247 cites W2150506239 @default.
• W2106872247 cites W2155180080 @default.
• W2106872247 cites W2157749483 @default.
• W2106872247 cites W2167310289 @default.
• W2106872247 cites W2167988999 @default.
• W2106872247 cites W2168607622 @default.
• W2106872247 cites W2168696662 @default.
• W2106872247 cites W2169362512 @default.
• W2106872247 doi "https://doi.org/10.1128/jvi.00214-14" @default.

• next