Cross-species virus transmission and the emergence of new epidemic diseases

Abstract

Host range is a viral property reflecting natural hosts that are infected either as part of a principal transmission cycle or, less commonly, as "spillover" infections into alternative hosts. Rarely, viruses gain the ability to spread efficiently within a new host that was not previously exposed or susceptible. These transfers involve either increased exposure or the acquisition of variations that allow them to overcome barriers to infection of the new hosts. In these cases, devastating outbreaks can result. Steps involved in transfers of viruses to new hosts include contact between the virus and the host, infection of an initial individual leading to amplification and an outbreak, and the generation within the original or new host of viral variants that have the ability to spread efficiently between individuals in populations of the new host. Here we review what is known about host switching leading to viral emergence from known examples, considering the evolutionary mechanisms, virus-host interactions, host range barriers to infection, and processes that allow efficient host-to-host transmission in the new host population.

FIG. 1.

(A) Known human influenza A pandemics. (B) Animal epidemic and pandemic strains, outbreaks, and human transfers in the past 60 years. Human pandemics of influenza include the related H1N1, H2N2, and H3N2 pandemics, while the transfers to other mammalian or avian hosts that have given rise to epidemic strains or that have resulted in human infection are also shown. More is known about the recent transfers to humans, and it is likely that previous transfers occurred but are not well characterized. Information taken from reference .

FIG. 2.

Diagrammatic representation of the steps involved in the emergence of host-switching viruses, showing the transfer of viruses into the new host (e.g., human) population with little or no transmission. An occasional virus gains the ability to spread in the new host (R₀ > 1), and under the right circumstances for transmission those viruses will emerge and create a new epidemic. (Adapted from reference with permission from Macmillan Publishers Ltd.)

FIG. 3.

The steps involved in the emergence of host-switching viruses, showing the host and viral processes that can be involved in the transfer and adaptation process (based on data from reference 149).

FIG. 4.

Some of the virus receptor changes involved in the virus-host interactions of the SARS coronavirus S protein, showing the variation of some residues that affect binding to the receptors (ACE2) from different hosts. (A) The distribution of S protein residues 479 and 487. (Top) The most frequently observed residues from sequences of viruses obtained during the human SARS CoV epidemic of 2002 and 2003, from sporadic infections from 2003 and 2004, and from palm civets in Guangdong, China. One palm civet virus (of >20 sequences examined) had Thr at 487, which is found in all human sequences from the 2002-2003 epidemic (>100 sequences). (Bottom) S-protein residues conferring efficient binding to the ACE2 proteins of the indicated species (the entry for reservoir species [likely bats] is speculative). GD03 and TOR2 are representative human strains of SARS CoV. (B) The contact region between the SARS CoV receptor binding domain and ACE2. Residues that convert rat ACE2 to an efficient receptor for SARS CoV are shown in orange. ACE2 lysine 31, which prevents association with SZ3 S protein, is shown in magenta. Lys (K) 31 and Lys (K) 353 are indicated by arrows, with the amino acids of palm civet, mouse, and rat ACE2 at these positions shown in parentheses. TOR2 S-protein residues Asn (N) 479 and Thr (T) 487 are also indicated, with the GD03 and SZ3 amino acids at these positions shown in parentheses. (Both panels reprinted from reference with permission.)

FIG. 5.

Origins of HIV-1 in humans from related viruses in chimpanzees, possible pathways of origin from other primates, and the possible roles of recombination. The three major types of HIV (N, M, and O) each derived from a separate transfer event. Cartoons showing three possible alternative routes of cross-species transmissions giving rise to chimpanzee SIV (SIVcpz) as a recombinant of different monkey-derived SIVs illustrate the possible complexity of the steps leading to the introduction of viruses into a new host. +Vif indicates the presence of an HIV-like Vif, which is required to overcome the effects of APOBEC3B. (A) Pan troglodytes troglodytes as the intermediate host. Recombination of two or more monkey-derived SIVs (likely SIVs from red-capped mangabeys [SIVrcm] and the greater spot-nosed monkeys [SIVgsn] or related SIVs) and possibly a third lineage requiring coinfection of an individual monkey with one or more SIVs. Chimpanzees have not been found to be infected by these viruses. (B) The SIVcpz recombinant develops and is maintained in a primate host that has yet to be identified, giving rise to the ancestor of the SIVcpz/HIV-1 lineage. P. t. troglodytes functions as a reservoir and was responsible for each of the human introductions. (C) Transfer through an intermediate host (yet to be identified) that is the current reservoir of introductions of SIVcpz into current communities of P. t. troglodytes and P. t. schweinfurthii as a potential source of diverse SIVcpz variants that are each found in limited geographic regions of Africa. (Reprinted from reference with permission of AAAS.)

FIG. 6.

Detection of recombination and estimation of a breakpoint within the genome of bat SARS-like CoV (Bt-SLCoV) strain Rp3. A similarity plot (A) and a bootscan analysis (B) detected a single recombination breakpoint at around the open reading frame 1b (ORF1b)/S junction. The human SARS-like CoV (Hu-SCoV) group includes strains Tor2 (AY274119), GD01 (AY278489), ZJ01 (AY297028), SZ3 (AY304486), GZ0402 (AY613947), and PC4 (AY613950). (C) Organization of ORFs of the SARS CoV genome and location of the estimated breakpoint. The blue and red horizontal arrows represent the essential ORFs from the major and minor parents, respectively. A sequence alignment of the ORF1b/S junction regions of SARS CoV strains Rp3, Tor2, and Rm1 is shown below. A consensus intergenic sequence (IGS) and the coding regions of ORF1b and S are annotated above the alignment. The black vertical arrow below the alignment indicates the estimated breakpoint located immediately after the start codon of the S coding region. nt, nucleotide. (Reprinted from reference with permission.)

FIG. 7.

Evolutionary models and examples of cross-species transmission of viruses. (A) Here the donor and recipient species represent two distinct fitness peaks for the virus which are separated by a steep fitness valley. Multiple adaptive mutations (circles) are therefore required for the virus to successfully replicate and establish onward transmission in the recipient host species. (B) The donor and recipient species are separated by a far shallower fitness valley. This facilitates successful cross-species transmission because only a small number of advantageous mutations are required. (Panels A and B adapted from reference with permission of AAAS.) (C) The emergence of CPV as an example of multiple mutations being required for a virus to adapt to a new host, after which the virus evolves within the recipient species. The phylogeny of the capsid protein gene shows only a single origin of all the CPVs. Viruses in the donor hosts include feline panleukopenia virus (FPV), mink enteritis virus (MEV), and the Arctic (blue) fox parvovirus (BFPV). In this example, there were two known host range adaptation steps where there were multiple mutations (indicated by circles). (D) A second form of host transfer, where there is a lower evolutionary barrier to cross-species transfer, allowed the establishment of the different HIV clades in humans, suggesting a lower barrier to transfer into the new host species. The example shows a phylogenetic analysis of polymerase genes from viruses of chimpanzee (SIVcpz) or human (HIV). Representative strains of HIV-1 groups M, N, and O and SIVcpz from P. t. schweinfurthii (SIVcpzTAN1, -TAN2, -TAN3, and -ANT) are shown. (Adapted from reference with permission of AAAS.)

FIG. 8.

SARS as an example of the global spread of a respiratory virus in humans after transfer from a zoonotic reservoir. The time line is of the SARS coronavirus global outbreak from the initial human infections in China in late 2002 to the global spread of the virus and the subsequent control of the spread of the virus in mid-2003. Numbers indicate the total number of confirmed cases in each country. (Adapted from reference with permission.)