Methods for studying molecular taxonomy and epidemiology of HIV
المؤلف:
Baijayantimala Mishra
المصدر:
Textbook of Medical Virology
الجزء والصفحة:
2nd Edition , p269-271
2025-12-15
35
The gold standard for determining the taxonomy and genotype of HIV is sequencing followed by phylogenetic analysis, which identifies the genotype as well as its relationship to reference sequences. In past, it relied mainly on partial genetic sequences of gene targets like env and gag. Partial gene sequencing and phylogenetic analysis had identified subtypes A to K, but a near complete genome sequencing followed by phylogenetic analysis has led to the conclusion that subtype E and subtype I were recombinants of subtype A and E and subtypes A, G, and unknown subtypes. Hence, more recently near complete genomes and whole genomes are being used to infer the molecular epidemiology and taxonomy of HIV.
Other methods that are used for molecular epidemiology include heteroduplex mobility assay, V-3 serotyping for HIV1 and subtype classification by PCR all of which are useful only in situations where a single subtype predominates in the community. Heteroduplex mobility assay exploits the difference in electrophoretic motility of heteroduplex formed between a PCR amplicon from reference strain and sample and is reliable for subtyping of HIV-1. V-3 serotyping is serological typing using patient’s sera which contain antibodies that bind to the peptides from a V 3 loop of envelop from different subtypes. It is a simple assay that depends on immune response to the small antigenic domain and even a single substitution can affect serotyping. V-3 serotyping has not been found to be useful in cases of HIV-2.
After partial or near complete or whole genome sequencing of the HIV isolates, phylogenetic software tools like the PhyloPlace (https://www.hiv.lanl.gov/ content/sequence/phyloplace/ PhyloPlace.html ) and subtyping distance tool (SUDI, https://www.hiv.lanl.gov/content/ sequence/SUDI/sudi.html) may be used for phylogenetic/taxonomical analysis. The above softwares have specially been created by the Los Alamos National Laboratory in collaboration with the National Institute of Health and Department of Health and Human Services, USA to help in deciding whether a given sequence or a set sequences belong to a known subtype, or is a new subtype, a sub subtype or a variant of an existing subtype. While analyzing phylogenetic data generated from software tools, there are no cut off rules on branching index values to decide whether a given sequence is a subtype or a variant. However, a thumb rule subtype specific branching index of 0.66 has been used following its evaluation by Hraber et al in 2008. Other softwares that are frequently used in phylogenetics/taxonomy studies include ClustaW, MEGA, and REGA HIV-1 Subtyping Tool: Version 3.0 (http://dbpartners. stan ford.edu:8080/RegaSubtyping/stanford-hiv/ typingtool/).
Importance of Studying HIV Molecular Epidemiology
HIV type 1 isolates worldwide exhibit huge genetic diversity as the virus possesses an error prone reverse transcription process without proofreading activity, recombination events between strains, immunological pressure, and a rapid turnover. The different types, subtypes, circulating recombinant forms differ in their rate of disease progression, susceptibility to anti-retroviral drugs, transmission dynamics, etc.
It is known that HIV type2 has a longer asymptomatic period, lower viral copy numbers, and a lower mortality as compared to HIV type1. Also, HIV-1 group O and HIV-2 isolates are intrinsically resistant to non nucleoside reverse transcriptase inhibitors. Among HIV-1 group M subtypes, subtype C strains have been observed to frequently use CCR5 co-receptor (more commonly) for entry into the host cells even in the late stages of HIV and switching to CXCR4 receptor use is extremely rare among the Indian subtype C strains. Hence, maraviroc a CCR5 inhibitor can be used for treatment of HIV in India. Although differences in antiretroviral drug susceptibility is observed among different subtypes of HIV-1, large studies have not found increased failure rates among the subtypes.
A study from Thailand has shown an increased probability of transmission of CRF01_AE among injection drug users as compared to subtype B, and another study from Tanzania demonstrated that subtype C showed a high in utero transmission compared to other subtypes. Further, the observation that the heterosexual route of transmission drives the AIDS pandemic in Africa and India it is speculated that subtype C especially suited for heterosexual route of transmission. However, since multiple factors play a role in transmission of the infection, it is difficult to pinpoint that the differences in rates of transmission are solely due to the subtype.
Knowledge of the circulating genotypes is essential for the development of a vaccine against HIV. The said vaccine should contain all the circulating forms or conserved epitopes of HIV to be effective prevention of the disease. Thus, study of molecular epidemiology of HIV is important to understand transmission dynamics, devising diagnostic tests, vaccines and public health control of HIV. Continued molecular epidemiological surveillance will help in tracking new infections, susceptible populations and effective delivery of preventive and/or therapeutic measures to contain the HIV pandemic.
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