Emergence of Novel Unique Recombinant Forms and Multiple Subtypes in Gag-Pol Region of HIV-1 in Punjab, Pakistan
Emergence of Novel Unique Recombinant Forms and Multiple Subtypes in Gag-Pol Region of HIV-1 in Punjab, Pakistan
Amreen Zahra1*, Mushtaq A. Saleem2, Hasnain Javed3, Muhammad Azmat Ullah Khan4 and Abdul Rauf Shakoori4
ABSTRACT
The current era faces a major health challenge of drug resistance and viral escape mutants of human immunodeficiency virus (HIV-1) worldwide. Therefore, a deep molecular insight unveiling the genetic characteristics of the prevailing strains is the need of the hour for successful disease control interventions in endemic countries like Pakistan. Here we present, a detailed molecular and computational analysis of the major genetic constituents, Gag-Pol region of HIV-1 for the very first time in Punjab-Pakistan including three regions of outbreak i.e. Kot Imrana Sargodha, Faisalabad and Gujrat. Drug resistance mutations such as T12A, I13A, K14R, I15V, K20I, T31S, E35D, M36I, N37D, R41K, K43X, R57K, Q61H, H69K, K70R and L89M were observed across several sites across the whole length of PR region among the isolates. A significant accessory resistance mutation V32I conferring a low level of resistance against non-nucleoside reverse transcriptase inhibitors was observed among two isolates. This kind of genotypic pattern demonstrated a striking evidence of multiple transmission routes and co-circulating viruses due to increased genetic diversity in Pakistani isolates. However, SNAP analyses demonstrated higher values for Subtype A1 and Subtype C denoting a positive selection pressure and sequence conservation among the HIV-1 isolates in Pakistan. Our phylogenetic analyses revealed that HIV subtype A1 was found to be the most predominant subtype found in Pakistani population with 30% ratio among the isolates, 10% was of CRF02_AG, Subtype C a potential recombinant had 3.33% and unique recombinant form URFs accounted for 13.3% in the HIV Gag sequences. All Pol (URFs) demonstrated 40% of ratio among the isolates, and Subtype D with 6.66%. The present study shows that multiple subtypes of HIV-1 are present in the affected population. Hence, this study highlights the demand of continuous future studies on disease surveillance coupled with responsible evaluation of drug resistance in HIV-1 at higher resolution. This study emphasizes on the sudden emergence of circulating HIV-1 subtypes and its deadly drug resistant variants in Pakistan in the recent years. However, such molecular approaches in developing nations like Pakistan, will pave favourable strategies for advanced drug design, diagnostic assays and antiretroviral regimen therapies.
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