Several papers published in Genome Announcements recently describe the sequences of new Zika virus isolates. Scientists have known the genomic sequence of at least one Zika virus isolate since 2007, but continue to publish newly isolated strains. What is the importance of these additional sequences?
Sequences from many sources are one of the most reliable tools to track the origin of an outbreak. When first described in 1947, Zika was found in Uganda, and later in other countries of sub-Saharan Africa, such as Tanzania, Nigeria, and Gabon. When the Micronesian island of Yap experienced an outbreak in the 2000s, the African source was fairly clear (although we now know that diagnostics may have misinterpreted possible Zika cases as Dengue). The sequencing results are less important when there are fewer outbreak sources, such as a geographically limited disease, but may prove essential in the instance of a quickly spreading disease.
Tracing an outbreak to its source becomes more complicated as the disease spreads. Determining the route of disease dissemination requires understanding travel patterns to institute measures to halt disease spread. Any country with air travel and infected mosquitos might see a case among tourists, who might in turn return to their home country, infected (and perhaps asymptomatic) and able to spread the disease to that region’s mosquitos. A Genome Announcement report by first author Lin Liu and senior scientist Dexin Li describes a complete Zika genome sequence resulting from a case of a recent traveler to Venezuela returning to China with subsequent Zika virus infection confirmed through RT-PCR. Phylogenetic analyses comparing the Chinese tourist viral genome to previously sequenced strains revealed that the traveler, returning from Venezuela, harbored a Zika virus strain closely related to the Asian lineage, which is related to the strains from the recent French Polynesian and Brazilian outbreaks (the other lineage is the African lineage; see figure, right).
Other important information can be obtained by analyzing the evolution of the strains as well. The sequence from the Chinese tourist revealed eleven amino acid residue changes in the E gene between the isolate and a previous Brazilian isolate. The E gene codes for the envelope protein of the virus and as one of the first points of contact with the immune system, has been a target for antiviral and vaccine targets. Furthermore, natural mutations can also be a starting point for scientists looking to explain pathological differences between viral strains. Critically, investigations into genomic differences, such as E gene mutations mentioned above, may also help pinpoint genetic changes that explain the microcephaly associated with Zika virus infection, first detected in Brazil, despite decades of Zika virus circulation elsewhere in the world.
Of course, the more genetic information one has, the more accurate phylogenetic analyses will be. However, generating an entire viral genome is still not trivial. Thankfully, this level of detail was accomplished in a second Genome Announcement report from first author Mariana Cunha and senior author Benedito da Fonseca: the first entire genome sequence of a Brazilian strain containing all open reading frames and the 5’ and 3’ untranslated regions. The Brazilian isolate, from a patient sickened through blood transfusion, is the first full-length genome sequenced from an autochthonous transmission within Brazil.
Zika virus, a member of the flavivirus family, is a (+)ssRNA virus. Its genome is 10.7 kilobases long, which codes for a single polyprotein (see figure, left). The polyprotein is processed into individual viral proteins that includes three structural proteins, a capsid protein, an envelope protein, a membrane-associated protein, and seven nonstructural proteins, and its full-length genome shows Zika genes have the same gene order as other flaviviruses. Investigations into genomic differences, such as E gene mutations mentioned above, may also help pinpoint genetic changes that may explain the microcephaly associated with Zika virus infection, first detected in Brazil despite decades of Zika virus circulation.
Genomic studies can go hand-in-hand with epidemiologic studies; a recently published report in Science ($) looked at genetic changes over time and concluded the virus has been in Brazil since 2013, earlier than previously hypothesized dates centered around the World Cup or other large-scale events. Generating an increasingly larger number of genomes like these in Genome Announcements will help researchers answer the questions of Zika virus history and pathogenicity.
-- Julie Wolf
Photo credits: Zika genome and phylogenetic tree