Method: Known and novel mutations were identified by comparing with NRTI-associated RNase H mutations previously identified from subtype B drug-resistance studies: K451R, D460N, L469F, T470N, T473A, N474A, Q475A, K476A/N, D488E, L491S, Q500A, Y501A/F, I505A, I506L, Q509L, K512Q, K527N, K530R, PMID: 22363673
2012
PloS one
Abstract: BACKGROUND: We previously demonstrated in vitro
Abstract: The goal of the current study was to determine whether AZT monotherapy in HIV-1 infected patients also selects the A371V, Q509L or other mutations in the C-terminal domains of HIV-1 RT.
Discussion: By contrast, the Q509L mutation was not present in any of the sequences.
Discussion: We previously reported that in in vitro selection experiments HIV-1 selected for two novel mutations - A371V in the connection domain and Q509L in the RNase H domain - in combination with D67N, K70R and T215F that together conferred greater than 100-fold AZT resistance.
Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy.
Introduction: Examples are E312Q, G335C/D, N348I, A360I/V, V365I and A376S in the HIV-1 RT connection subdomain, and Q509L, H539N and D549N in the RNase H domain.
Discussion: Thus, mutations such as N348I, A360V and Q509L increased chain-terminated primer rescue with RNA/DNA complexes, but not with DNA/DNA template-primers.
N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations.
Introduction: In this regard, A371V and Q509L in the connection and RNase H domains, respectively, and mutations located at residues that form part of the RNase H primer grip potentiate resistance to tenofovir in cell culture based assays when combined with TAMs.
Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients.
Abstract: However, N348I, A376S and Q509L did confer varying amounts of nevirapine resistance by themselves, even in the absence of EEMs.
Discussion: Although Q509L was not observed in our cohort, this mutation was found in the pretreated patients of another survey (n=118).
Discussion: Furthermore, the G333D, G335C, N348I, A360I/V and
Discussion: However, site directed mutagenesis studies showed that G333D, G335C, A360I/V and Q509L did not confer significant AZT resistance in the absence of other AZT resistance mutations.
Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms.
PMID: 18547911
2008
The Journal of biological chemistry
Introduction: In addition, A371V and Q509L in the RNase H domain emerge under the selective pressure of AZT in cell culture.
Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance.
Result: The enzymes included in this study were WT RT, D67N/K70R/T215F (AZTR) RT, and AZTR/Q509L RT.
Result: There was also a significant decrease in the rate of appearance of a cleavage event that reduces the RNA/DNA duplex length to 10 n
Result: These results reinforce the findings described in Figure 1 and further demonstrate that the Q509L mutation augments zidovudine resistance on an RNA/DNA T/P but not a DNA/DNA T/P.
Result: Thus, these studies did not inform if Q509L also affected the primary RNase H cleavage event, which occurs in the millisecond time range, or the sequence of cleavage and T/P dissociation events that generate the 19 nt RNA product.
Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3'-azido-3'-dideoxythymidine.
Abstract: A371V and Q509L also increased cross-resistance with TAMs to lamivudine and abacavir, but not stavudine or didanosine.
Abstract: The first resistance mutations to appear in HIV-1(LAI) were two polymerase domain thymidine analog mutations (TAMs), D67N and K70R, and two novel mutations, A371V in the connection domain and Q509L in the RNase H domain, that together conferred up to 90-fold AZT resistance.
Abstract: The roles of A371V and Q509L in AZT resistance were confirmed by site-directed mutagenesis: A371V and Q509L together increased AZT resistance approximately 10- to 50-fold in combinat
N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance.
Introduction: Finally, a recent study reported that A371V in the connection domain and Q509L in the RNase H domain of HIV-1 RT were selected in combination with TAMs when virus was passaged under increasing concentrations of AZT.
HIV mutation literature information.
PMID: 
2017
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