The role of translation error for Escherichia coli individual beta-galactosidase molecule catalytic and electrophoretic heterogeneity was investigated using CE-LIF. An E. coli rpsL mutant with a hyperaccurate translation phenotype produced enzyme molecules that exhibited significantly less catalytic heterogeneity but no reduction of electrophoretic heterogeneity. Enzyme expressed with streptomycin-induced translation error had increased thermolability, lower activity, and no significant change to catalytic or electrophoretic heterogeneity. Modeling of the electrophoretic behaviour of beta-galactosidase suggested that variation of the hydrodynamic radius may be the most significant contributor to electrophoretic heterogeneity.
As of February 2012, 50 circulating recombinant forms (CRFs) have been reported for HIV-1 while one CRF for HIV-2. Also according to HIV sequence compendium 2011, the HIV sequence database is replete with 414,398 sequences. The fact that there are CRFs, which are an amalgamation of sequences derived from six or more subtypes (CRF27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent evolution of the virus with its approximate 1% per year rate of evolution, and this phenomena per se poses tremendous challenge for vaccine development against HIV/AIDS, a devastating disease that has killed 1.8 million patients in 2010. Here, we explore the interaction between HIV-1 and host genetic variation in the context of HIV/AIDS and antiretroviral therapy response.
Sub-Saharan Africa accounts for 69% of the people living with HIV globally. An estimated 1,600,000 Kenyans are living with HIV-1. Antiretroviral therapy (ART) has saved 9 million life-years in Sub-Saharan Africa. However, drug resistance mutations reduce the effectiveness of ART, and need to be monitored for effective ART. Naturally occurring primary antiretroviral drug resistance mutations have not been well analyzed in ART naïve HIV+ patients in Kenya. Here we have examined protease inhibitor (PI) resistance mutations in ART naïve HIV-1 seropositive women in Pumwani sex worker cohort established in Nairobi, Kenya, wherein HIV-1 infection is predominantly caused by subtypes A and D viruses. We have analyzed consensus sequences of HIV protease from 109 drugnaïve patients, as a part of HIV-1 whole-genome sequencing using 454 sequencing methodology. Analysis using HIVdb program revealed a prevalence of 22% (24/109) PI resistance mutations among the study subjects. D30N (3.7%), M46I (0.9%) and V82F (0.9%) are the major mutations observed. D30N mutation is known to confer high-level resistance to nelfinavir. M46I and V82F confer resistance to indinavir, lopinavir, fosamprenavir and nelfinavir. In addition, many minor mutations were found at seven different drug resistance sites. It is important to study the implications of these mutations to the effectiveness of specific PI drug treatment. This study provides valuable data pertaining to primary drug resistance in Kenyan HIV-1 infected patients before ART became available.
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