Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China

Abstract

To explore the evolutionary dynamics and molecular transmission patterns of HIV-1 CRF01_AE in depth among men who have sex with men (MSM) in Shanghai, we constructed phylogenetic tree and genetic transmission networks based on 1, 152 pol sequences from MSM, 282 from other risk groups and 795 references. Phylogenetic analyses identified two distinct major CRF01_AE lineages and a Shanghai-based sub-lineage. The estimated tMRCAs for lineage 1 and 2 were 1996.0 (1992.9–1999.2) and 1997.8 (1994.3–2001.4), respectively. Of the 1, 152 MSM, 681 (59.1%) were identified as belonging to 241 separate networks. Of these 681 individuals in networks, 74.2% were linked to cases diagnosed in different years, 4.3% were linked to heterosexual women, and 0.7% were linked to persons who inject drugs. A total of 71 networks including 180 individuals diagnosed in Shanghai with the same domicile were found. Recent infection (P = 0.022) and sampling year after 2011 (P < 0.001) were significantly associated with potential transmission links among the networks. Besides, a significant transmission of viruses with drug resistant mutations at V179D/E were found in the networks. Given these findings, we propose that genetic transmission analysis is a useful tool in HIV intervention strategies to curb the spread of virus and promoting public health.

Genetic transmission networks reveal the transmission patterns of HIV-1 CRF01_AE in China

“…We observed that individuals with multiple links represented only a minority of persons but were involved in most of the persons in network. This result was similar to our previous results in Shanghai and confirmed that a few ‘core population’ indeed drive transmission networks to a significant extent 9. Identifying and controlling these ‘core population’ is therefore crucial for curbing HIV spread in a population 24 25.…”

“…w6 Several studies indicated that migrants accounted for a large proportion of HIV epidemic in China 16, w7 and posed a persistent increase among newly diagnosed HIV infections every year in some areas 4 16 26. Our previous observation suggested ongoing transmission of CRF01_AE strain between Shanghai city and other provinces, for which migrants played a crucial role 9. In this in-depth observation at national level, we expanded the number of available sequences and revealed that large-scale population migration between China’s provinces undoubtedly facilitated viral transmission.…”

“…The flow chart of genetic transmission network analysis included four steps: phylogenetic tree construction, transmission cluster extraction, minimum genetic distance identification and network visualisation 9. Cluster Picker10 was used to extract transmission clusters from the phylogenetic tree, with the intracluster maximum pairwise distance <3.0% nt substitutions per site and bootstrap support value ≥95%.…”

“…The Tamura-Nei 93 pairwise genetic distances of all sequences within the available clusters were calculated in Mega V.7.0. Among all distances, one that minimises the sum of edge weights (genetic distances) was selected to define the linkages within a cluster 9. Lastly, the network data were visualised and analysed using a custom R script using the network package in the R software 11…”

“…The understanding of transmission networks focuses on genetic similarity of sequences and has the capacity to identify potential transmission partners and recognise the links between different populations 8. Recently, we reported genetic transmission networks for CRF01_AE-infected MSM in Shanghai, preliminarily revealing transmission both inside Shanghai and between Shanghai and several neighbouring provinces 9. However, the genetic transmission networks of CRF01_AE at the national level have not been clearly characterised.…”