HIV-1 subtype kindergarden Hauke Walter Arevir 2015 HIV-1 subtype - - PowerPoint PPT Presentation

HIV-1 subtype kindergarden

Hauke Walter Arevir 2015

HIV-1 subtype distribution

Source: Is HIV-1 evolving to a less virulent form in humans? Kevin K. Ariën, Guido Vanham and Eric J. Arts Nature Reviews Microbiology 5, 141-151 (February 2007)

Relevance of HIV subtyping

• Low level of relevance

– Diagnosis and therapy monitoring – Laboratory: done by the way (resistance test)

• High level of relevance

– Epidemiological observations – Vaccine research

Personal Impression: increasing problems while subtyping by the way to identify subtype Check …

Subtyping tools – how are you?

• Stanford hivDB subtyping tool last update?

– Hard to find: 2002

• NCBI last update 2009, no more funding
• HIV-GRADE subtyping is a copy of hivDB subtyping

– Last update 2009 (minimal changes)

• Geno2pheno - … ? (many different variants....)
• Rega (Belgian system, but samples often without result)
• Comet (maybe best today, but no resistence testing,

last update 2014)

Feeling to facts - methods

• 651 samples for resistance analysis

– 02/2014 – 01/2015

• Fasta analysed by HIV-GRADE subtyping tool

– discrepant subtyping result for PR and RT

 re-analyzed by

 NCBI subtyping tool (each 300bp analyzed in 100bp steps; (http://www.ncbi.nlm.nih.gov/projects/genotyping/genotype.cgi)  COMET tool (http://www.hiv.lanl.gov/content/sequence/HIV/CRFs/CRFs.html)  Manual comparison in CRF list (http://www.hiv.lanl.gov/content/sequence/HIV/CRFs/CRFs.html)

Feeling to facts - results

– Distribution typically for Germany – MIST = discrepant subtype in PR and RT by HIV-GRADE

651 Total 59 (9.1%) MIST 11 A 478 B 23 CRF01_AE 29 CRF02_AG 34 C 5 D 4 F 8 G

Subytping discrepancies in HIV GRADE - overview

RT PR A B CRF01 _AE CRF02 _AG C D F G H K A 25 2 1 B 1 CRF01_AE 3 1 1 CRF02_AG 1 1 2 C D 12 1 1 F 1 G 3 1 J 1 K 1

Examples

• COMET: B

CRF03_AB

HIV-GRADE and NCBI clearly B (10387515) HIV-GRADE: CRF01_AE or B NCBI: CRF03_AB (10390017)

Examples NCBI salad

HIV-GRADE: B or CRF01_AE NCBI CRF list: NCBI: CRF33_01B or CRF15_01B  COMET: CRF33_01B

(ID: 30195430)

Examples NCBI salad

HIV GRADE: A oder CRF01_AE NCBI: CRF03_AB/CRF01_AE/ CRF15_01B/A  COMET: A1

(10386227)

Examples NCBI salad

HIV GRADE: D oder B NCBI:  COMET: unassigned; D, 29_BF  Patient from Brasilia: CRF29_BF

(10383311)

Examples NCBI salad

HIV GRADE: F or B NCBI: many BF`s  COMET: unassigned_1;29_BF, F1, B  Clade BF ?

(10369869)

Examples NCBI salad

HIV-GRADE: NCBI: D/A/CRF15-01B/CRF_35_AD A mit niedriger Homologie (< 92%)  COMET: unassigned_1;10_CD, A1 ???

(10379034)

D A1

Subtyping discrepancies in NCBI -

• verview

Summary

• 59 of 651 (9,1%) fastas discrepant subtypes for

PR/RT by GRADE

• 46 of 59 are A/CRF02 and D/B mixtures and

some more A/A1/CRF01_AG/CRF02_AG....

– Easy to solve

• Remaining 13 (2.3% of all) of all GRADE

subtyping discrepancies were harder to identify

– 5 strains were unassigned by all tools

Discussion

• Couldn‘t it be better?
• Somebody interested (maybe MPI?)
• Implications for

– vaccination strategies (has to be up to date, identification of new

variants possible, old stuctures are confusing  need for a new classification system e.g. like clade BF_brasil and clade BG_cuba?

– Transferable for other viruses???  HCV problem: need to know genotype before resistence testing

can be done (variability !; generate methods: Alignment and genotyping)

– …?

Thank You

Comet results

name virus subtype 15StN_30195430_HIV2835B30195430.0.3 HIV-1 33_01B 30StN_10386227_HIV2715B10386227.0.2 HIV-1 A1 21StN_10383311_HIV2715B10383311.0.1 HIV-1 unassigned_2;D, 29_BF 27StN_10379034_HIV2835B10379034.0.2 HIV-1 unassigned_1;10_CD, A1 03StN_10369869_HIV2835B10369869.0.3 HIV-1 unassigned_1;29_BF, F1, B