Sharma Shilpee, Aralaguppe Shambhu G, Abrahams Melissa-Rose, Williamson Carolyn, Gray Clive, Balakrishnan Pachamuthu, Saravanan Shanmugam, Murugavel Kailapuri G, Solomon Suniti, Ranga Udaykumar
Jawaharlal Nehru Centre for Advanced Scientific Research, HIV-AIDS Laboratory, Jakkur (PO), Bangalore, 560 064, India.
Division of Medical Virology and Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, and National Health Laboratory Service, Cape Town, South Africa.
BMC Infect Dis. 2017 Jan 24;17(1):95. doi: 10.1186/s12879-017-2184-4.
HIV-1 subtype C demonstrates several biological properties distinct from other viral subtypes. One such variation is the duplication of PTAP motif in p6 Gag. PTAP motif is a key player in viral budding. Here, we studied the prevalence of PTAP motif duplication in subtype C viral strains in a longitudinal study.
In a prospective follow-up study, 65 HIV-1 seropositive drug-naive subjects were monitored in two different clinical cohorts of India for 2 years with repeated sampling at 6-month intervals. The viral RNA was extracted from plasma, the gag segment was amplified and sequenced. From a subset of viral isolates the sequences of pol, env and LTR were sequenced. Using HIV-1 gag amino acid sequences available from public databases and additional sequences derived from the Indian and South-African cohorts, we examined the nature of PTAP motif duplication in subtype C.
In 16% (8 of 50) of the primary viral strains of India, we identified a sequence duplication of the PTAP motif in Gag p6. The length of the sequence duplication varied from 6 to 14 amino acids in the viral isolates but remained fixed within a subject over a period of 24-36 month follow-up. In the duplicated motif, the core PTAP motif was invariable, but the flanking residues were highly variable. In an acute phase clinical cohort of South Africa, in a subset of 75 subjects, we found the presence of the PTAP duplication at a frequency of 29.3%. An analysis of the gag sequences from the extant databases showed that unlike other subtypes of HIV-1, subtype C has a natural propensity to generate the PTAP motif duplication at a significantly higher frequency and of greater length. Additionally, the global prevalence of PTAP duplication in subtype C appears to be increasing progressively over the past 30 years.
We showed that in subtype C, the duplication of the PTAP motif in p6 Gag involves sequence stretches of greater length, and at a much higher frequency as compared to other HIV-1 subtypes. Given that subtype C naturally lacks the Alix binding motif, the acquisition of an additional PTAP motif may confer replication advantage on this HIV-1 subtype. Further investigation is warranted to examine the significance of PTAP motif duplication on the replicative fitness of HIV-1.
HIV-1 C亚型具有一些与其他病毒亚型不同的生物学特性。其中一种变异是p6 Gag中PTAP基序的重复。PTAP基序是病毒出芽的关键因素。在此，我们在一项纵向研究中对C亚型病毒株中PTAP基序重复的流行情况进行了研究。
在一项前瞻性随访研究中，对印度两个不同临床队列中的65名HIV-1血清阳性初治患者进行了为期2年的监测，每隔6个月重复采样。从血浆中提取病毒RNA，扩增并测序gag片段。从一部分病毒分离株中对pol、env和LTR序列进行测序。利用公共数据库中可获得的HIV-1 gag氨基酸序列以及来自印度和南非队列的其他序列，我们研究了C亚型中PTAP基序重复的性质。
在印度的16%（50株中的8株）原发性病毒株中，我们在Gag p6中鉴定出PTAP基序的序列重复。在病毒分离株中，序列重复的长度从6到14个氨基酸不等，但在24至36个月的随访期内，在一名受试者体内保持稳定。在重复的基序中，核心PTAP基序不变，但侧翼残基高度可变。在南非的一个急性期临床队列中，在75名受试者的一个亚组中，我们发现PTAP重复的存在频率为29.3%。对现有数据库中gag序列的分析表明，与HIV-1的其他亚型不同，C亚型天然倾向于以显著更高的频率和更长的长度产生PTAP基序重复。此外，在过去30年中，C亚型中PTAP重复的全球流行率似乎在逐渐上升。
我们表明，在C亚型中，p6 Gag中PTAP基序的重复涉及更长的序列延伸，并且与其他HIV-1亚型相比频率更高。鉴于C亚型天然缺乏Alix结合基序，则额外获得一个PTAP基序可能赋予该HIV-1亚型复制优势。有必要进行进一步研究以检验PTAP基序重复对HIV-1复制适应性的意义。
