Caio C. M. Freire

Spread of the pandemic Zika virus lineage is associated with NS1 codon usage adaptation in humans

Zika virus (ZIKV) infections were more common in the zoonotic cycle until the end of the 20th century with few human cases in Africa and Southeastern Asia. Recently, the Asian lineage of ZIKV is spreading along human-to-human chains of transmission in the Pacific Islands and in South America. To better understand its recent urban expansion, we compared genetic differences among the lineages. Herein we show that the recent Asian lineage spread is associated with significant NS1 codon usage adaptation to human housekeeping genes, which could facilitate viral replication and increase viral titers. These findings were supported by a significant correlation with growth in Malthusian fitness. Furthermore, we predicted several epitopes in the NS1 protein that are shared between ZIKV and Dengue. Our results imply in a significant dependence of the recent human ZIKV spread on NS1 translational selection.

Phylogeography of Rift Valley Fever Virus in Africa Reveals Multiple Introductions in Senegal and Mauritania

Rift Valley Fever (RVF) virus (Family Bunyaviridae) is an arthropod-borne RNA virus that infects primarily domestic ruminants and occasionally humans. RVF epizootics are characterized by numerous abortions and mortality among young animals. In humans, the illness is usually characterized by a mild self-limited febrile illness, which could progress to more serious complications. RVF virus is widespread and endemic in many regions of Africa. In Western Africa, several outbreaks have been reported since 1987 when the first major one occurred at the frontier of Senegal and Mauritania. Aiming to evaluate the spreading and molecular epidemiology in these countries, RVFV isolates from 1944 to 2008 obtained from 18 localities in Senegal and Mauritania and 15 other countries were investigated. Our results suggest that a more intense viral activity possibly took place during the last century compared to the recent past and that at least 5 introductions of RVFV took place in Senegal and Mauritania from distant African regions. Moreover, Barkedji in Senegal was possibly a hub associated with the three distinct entries of RVFV in West Africa.

Molecular phylogeography of tick-borne encephalitis virus in central Europe.

In order to obtain a better understanding of tick-borne encephalitis virus (TBEV) strain movements in central Europe the E gene sequences of 102 TBEV strains collected from 1953 to 2011 at 38 sites in the Czech Republic, Slovakia, Austria and Germany were determined. Bayesian analysis suggests a 350-year history of evolution and spread in central Europe of two main lineages, A and B. In contrast to the east to west spread at the Eurasian continent level, local central European spreading patterns suggest historic west to east spread followed by more recent east to west spread. The phylogenetic and network analyses indicate TBEV ingressions from the Czech Republic and Slovakia into Germany via landscape features (Danube river system), biogenic factors (birds, red deer) and anthropogenic factors. The identification of endemic foci showing local genetic diversity is of paramount importance to the field as these will be a prerequisite for in-depth analysis of focal TBEV maintenance and long-distance TBEV spread.

Tracing the Origin and Northward Dissemination Dynamics of HIV-1 Subtype C in Brazil

Previous studies indicate that the HIV-1 subtype C epidemic in southern Brazil was initiated by the introduction of a single founder strain probably originating from east Africa. However, the exact country of origin of such a founder strain as well as the origin of the subtype C viruses detected outside the Brazilian southern region remains unknown. HIV-1 subtype C pol sequences isolated in the southern, southeastern and central-western Brazilian regions (n = 209) were compared with a large number (n ~ 2,000) of subtype C pol sequences of African origin. Maximum-likelihood analyses revealed that most HIV-1 subtype C Brazilian sequences branched in a single monophyletic clade (CBR-I), nested within a larger monophyletic lineage characteristic of east Africa. Bayesian analyses indicate that the CBR-I clade most probably originated in Burundi and was introduced into the Paraná state (southern region) around the middle 1970s, after which it rapidly disseminated to neighboring regions. The states of Paraná and Santa Catarina have been the most important hubs of subtype C dissemination, and routine travel and spatial accessibility seems to have been the major driving forces of this process. Five additional introductions of HIV-1 subtype C strains probably originated in eastern (n = 2), southern (n = 2) and central (n = 1) African countries were detected in the Rio de Janeiro state (southeastern region). These results indicate a continuous influx of HIV-1 subtype C strains of African origin into Brazil and also unveil the existence of unrecognized transmission networks linking this country to east Africa.

Reemergence of Rift Valley fever, Mauritania, 2010.

A Rift Valley fever (RVF) outbreak in humans and animals occurred in Mauritania in 2010. Thirty cases of RVF in humans and 3 deaths were identified. RVFV isolates were recovered from humans, camels, sheep, goats, and Culex antennatus mosquitoes. Phylogenetic analysis of isolates indicated a virus origin from western Africa.

Modularity and evolutionary constraints in a baculovirus gene regulatory network

BackgroundThe structure of regulatory networks remains an open question in our understanding of complex biological systems. Interactions during complete viral life cycles present unique opportunities to understand how host-parasite network take shape and behave. The Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) is a large double-stranded DNA virus, whose genome may encode for 152 open reading frames (ORFs). Here we present the analysis of the ordered cascade of the AgMNPV gene expression.ResultsWe observed an earlier onset of the expression than previously reported for other baculoviruses, especially for genes involved in DNA replication. Most ORFs were expressed at higher levels in a more permissive host cell line. Genes with more than one copy in the genome had distinct expression profiles, which could indicate the acquisition of new functionalities. The transcription gene regulatory network (GRN) for 149 ORFs had a modular topology comprising five communities of highly interconnected nodes that separated key genes that are functionally related on different communities, possibly maximizing redundancy and GRN robustness by compartmentalization of important functions. Core conserved functions showed expression synchronicity, distinct GRN features and significantly less genetic diversity, consistent with evolutionary constraints imposed in key elements of biological systems. This reduced genetic diversity also had a positive correlation with the importance of the gene in our estimated GRN, supporting a relationship between phylogenetic data of baculovirus genes and network features inferred from expression data. We also observed that gene arrangement in overlapping transcripts was conserved among related baculoviruses, suggesting a principle of genome organization.ConclusionsAlbeit with a reduced number of nodes (149), the AgMNPV GRN had a topology and key characteristics similar to those observed in complex cellular organisms, which indicates that modularity may be a general feature of biological gene regulatory networks.

Reassortment and distinct evolutionary dynamics of Rift Valley Fever virus genomic segments

Rift Valley Fever virus (RVFV) is a member of Bunyaviridae family that causes a febrile disease affecting mainly ruminants and occasionally humans in Africa, with symptoms that range from mid to severe. RVFV has a tri-segmented ssRNA genome that permits reassortment and could generate more virulent strains. In this study, we reveal the importance of reassortment for RVFV evolution using viral gene genealogy inference and phylodynamics. We uncovered seven events of reassortment that originated RVFV lineages with discordant origins among segments. Moreover, we also found that despite similar selection regimens, the three segments have distinct evolutionary dynamics; the longer segment L evolves at a significant lower rate. Episodes of discordance between population size estimates per segment also coincided with reassortment dating. Our results show that RVFV segments are decoupled enough to have distinct demographic histories and to evolve under different molecular rates.

Does adaptation to vertebrate codon usage relate to flavivirus emergence potential

Codon adaptation index (CAI) is a measure of synonymous codon usage biases given a usage reference. Through mutation, selection, and drift, viruses can optimize their replication efficiency and produce more offspring, which could increase the chance of secondary transmission. To evaluate how higher CAI towards the host has been associated with higher viral titers, we explored temporal trends of several historic and extensively sequenced zoonotic flaviviruses and relationships within the genus itself. To showcase evolutionary and epidemiological relationships associated with silent, adaptive synonymous changes of viruses, we used codon usage tables from human housekeeping and antiviral immune genes, as well as tables from arthropod vectors and vertebrate species involved in the flavivirus maintenance cycle. We argue that temporal trends of CAI changes could lead to a better understanding of zoonotic emergences, evolutionary dynamics, and host adaptation. CAI appears to help illustrate historically relevant trends of well-characterized viruses, in different viral species and genetic diversity within a single species. CAI can be a useful tool together with in vivo and in vitro kinetics, phylodynamics, and additional functional genomics studies to better understand species trafficking and viral emergence in a new host.

Molecular evolution of Zika virus, an neglected emerging disease in Africa and Asia

Zika virus (ZIKV) is an arbovirus transmitted by mosquitoes isolated for the first time in Zika forest, Uganda in 1947 and repeatedly isolated in sub-Saharan Africa and South East Asia. Until 2000, only few human cases were reported but in 2007, the first major human outbreak was notified in Yap Island, Micronesia leading to 99 cases. Despite the widespread distribution of Zika virus, very limited information is available on the genetic relationship between the circulating strains. Therefore, we undertook a study on phylogeny and phylodynamics ZIKV in Africa and Asia. Partial and full length genome sequences of 38 strains from Senegal, Ivory Coast, Burkina Faso, Central African Republic and Malaysia were analysed. Phylogenetic reconstructions and datation were performed while recombination and viral population migrations were investigated. Phylogenetic analysis of the E, NS5 and NS5/3’NC gene showed two distinct ZIKV lineages circulating in Africa and a third lineage formed by the Micronesia and Malaysia strains. Besides, analysis of full length genome sequence allows identification of 5 recombinants isolates in Senegal and Ivory Coast. The 3 gene regions sequences evolved at a average rate of 7.74 x 10-4 nucleotide substitutions per site per year. Using the same analysis, we inferred that the most recent common ancestor of all ZIKV samples could be trace 325 years ago. The virus may have arrived in West Africa around 300 years before the present. And the migration rates showed considerable movements of ZIKV between Senegal to Ivory Coast and also to the other countries of East and central Africa. In conclusion, our study confirms previous observations showing divergences between Africa ZIKV isolate from Asia and the evidence of recombinants strains. Asian strains may represent a divergent lineage related to a common ancestor with spread throughout Southeast Asia and the Pacific from Africa.