Cache Valley virus
A mosquito-borne virus causing fetal loss in livestock and rare human encephalitis.
Cache Valley virus (CVV) belongs to the Bunyaviricetes class, the Orthobunyavirus genus, and the Bunyamwera serogroup. It was first identified in 1956 from *Culiseta inornata* mosquitoes collected in Utah’s Cache Valley. The virus is enveloped, roughly 80–120 nanometers in diameter, and carries a genome made up of three single-stranded RNA segments with negative-sense polarity. The large segment, about 6800 bases long in related bunyaviruses, codes for a probable viral polymerase. The medium segment is 4463 nucleotides in length, while the smallest segment encodes the nucleocapsid protein and a second non-structural protein. CVV has triggered outbreaks of spontaneous abortion and birth defects in ruminants like sheep and cattle. Human infections are rare, but when they occur, they can lead to encephalitis and multiorgan failure.
**Virology**
**Genome** The CVV genome is divided into three segments: small, medium, and large, named for their length. The large segment produces the L protein, an RNA-dependent RNA polymerase. The small segment uses overlapping reading frames to generate two proteins: the nucleocapsid protein N, and a non-structural protein called NSs. The medium segment codes for two type 1 transmembrane glycoproteins, Gn and Gc, plus a non-structural protein Nsm. Gn and Gc are initially made as one precursor protein, then cleaved during translation and modified by N-linked glycosylation.
**Replication cycle** The specific steps of CVV attachment, entry, replication, and release have not been studied directly. However, the replication cycle is understood for the *Orthobunyavirus* genus, which includes CVV. On the virus surface, Gn and Gc form spikes as a heterodimer, helping with attachment to host cells and membrane fusion. After entering the cell, the viral membrane merges with the endosomal membrane, releasing the genome. Transcription, driven by the RNA-dependent RNA polymerase, happens in the cytoplasm and is stopped by a strong hairpin loop sequence at the end of each genome segment. Once replication is complete, new virions are assembled and bud from Golgi apparatus membranes.
**Host interactions** Little is known specifically about how CVV regulates host processes or interacts with host cells. But within the Bunyamwera serogroup, two non-structural proteins are key during infection. In Bunyamwera vir
- vector
- mosquitoes (primarily Culiseta inornata)
Lore & Background
In ruminants, CVV is the most common orthobunyavirus in North America. It was linked to disease in 1987 during a large occurrence of aborted and malformed lambs in a Texas sheep flock. Infection in pregnant sheep can cause embryonic death or fetal malformations depending on gestation stage. Deer act as amplifying hosts, with high seroprevalence and viremia lasting 1 to 3 days, spreading the virus to mosquitoes.
Reader's Guide
Cache Valley virus is significant as a cause of reproductive losses in livestock, particularly sheep and cattle, and as a rare but severe human pathogen. Its first isolation in 1956 from Utah mosquitos established it as a member of the Bunyamwera serogroup. The virus's tripartite genome and its non-structural proteins, especially NSs, play roles in pathogenesis by inhibiting host protein synthesis and antiviral responses in mammalian cells, though not in mosquito cells. Human cases are extremely rare, with only three confirmed instances, two resulting in aseptic meningitis and one fatal case with encephalitis and multiorgan failure. The virus is likely underdiagnosed due to limited testing. Its wide geographic distribution and multiple mosquito vectors suggest that some unexplained cases of severe multiorgan failure, congenital anomalies, or encephalitis may be due to CVV. The virus's impact on livestock, particularly through abortion and congenital malformations, underscores its economic importance. Further research is needed to understand its full clinical range and true incidence.
Did You Know?
- Cache Valley virus was first isolated in 1956 from Culiseta inornata mosquitos collected in Utah's Cache Valley.
- Only three human cases of CVV disease have been confirmed, with one fatal case involving encephalitis and multiorgan failure.
- CVV is the most common orthobunyavirus in North America and was first linked to disease in sheep in Texas in 1987.
- Deer have a very high seroprevalence for CVV and act as amplifying hosts, with viremia lasting 1 to 3 days.
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